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Introduction: PICALM-MLLT10, formerly CALM-AF10, is a rarely reported fusion gene in hematological malignancies, especially in Asian people. Case presentations: Six patients with PICALM-MALLT10 fusion gene were identified at the First Affiliated Hospital, Zhejiang University School of Medicine, China between October 2019 and October 2023, with a median age of 25 years. Clinical diagnoses included acute myeloid leukemia (AML) in 2 patients, acute lymphoblastic leukemia (ALL) in 3, and mixed phenotype acute leukemia (MPAL) in 1. The prognosis of the patients was poor, and three patients died within 1 year despite of intensive treatment. Conclusion: Patients with PLCALM-MALLT10 can be diagnosed as AML, ALL, MPAL, and other extremely rare hematological malignancies, with mixed clinical manifestations and poor survival. Novel and intensive therapies, including hematopoietic stem cell transplantation, chimeric antigen receptor T-cell immunotherapy, and targeted agents such as the Bcl-2 inhibitor, could be considered in the future. [ABSTRACT FROM AUTHOR]

Mixed-phenotype acute leukemia (MPAL) is characterized by the expression of markers from multiple hematopoietic lineages, including myeloid, B-cell, and T-cell origins. This case report describes a 3-year, 8-month-old girl who presented with swelling in both eyes, initially accompanied by lumps on the neck and a fever that subsided with antipyretics. After the neck lumps resolved, eye swelling began in the right eye and later progressed to the left eye. Bone marrow aspiration confirmed the presence of mixed-lineage leukemia, revealing myeloblasts with Auer rod, monoblast, and lymphoblast. Leukemia phenotyping identified a mixed lineage involving myeloid, B-cell, and T-cell markers, supporting the diagnosis of MPAL. The patient was treated according to the acute lymphoblastic leukemia induction therapy protocol with vincristine and daunorubicin, and fluid hydration and allopurinol were taken to prevent tumor lysis syndrome. This case highlights the diagnostic complexity and need for a comprehensive treatment approach in managing MPAL.

Abstract Mixed‐phenotype acute leukemia (MPAL) with FLT3‐TKD mutations is a rare and challenging subtype of leukemia. Effective management strategies are crucial for improving patient outcomes. A 31‐year‐old man with FLT3‐TKD‐mutated MPAL achieved hematological remission through the JALSG ALL202‐O protocol and gilteritinib, followed by cord blood transplantation (CBT). Post‐transplant complications included adenovirus‐induced hemorrhagic cystitis, managed with bladder irrigation and ribavirin, and engraftment failure, necessitating a second CBT on Day 35. Subsequent adenoviral conjunctivitis resolved with vidarabine. The patient achieved neutrophil engraftment by Day 76 and was discharged on Day 173 without relapse. This case highlights the importance of vigilant supportive care and tailored therapy in managing MPAL with FLT3 mutations, especially in the context of post‐transplant complications.

Mixed-phenotype acute leukemia (MPAL) is characterized by the expression of markers from multiple hematopoietic lineages, including myeloid, B-cell, and T-cell origins. This case report describes a 3-year, 8-month-old girl who presented with swelling in both eyes, initially accompanied by lumps on the neck and a fever that subsided with antipyretics. After the neck lumps resolved, eye swelling began in the right eye and later progressed to the left eye. Bone marrow aspiration confirmed the presence of mixed-lineage leukemia, revealing myeloblasts with Auer rod, monoblast, and lymphoblast. Leukemia phenotyping identified a mixed lineage involving myeloid, B-cell, and T-cell markers, supporting the diagnosis of MPAL. The patient was treated according to the acute lymphoblastic leukemia induction therapy protocol with vincristine and daunorubicin, and fluid hydration and allopurinol were taken to prevent tumor lysis syndrome. This case highlights the diagnostic complexity and need for a comprehensive treatment approach in managing MPAL. [ABSTRACT FROM AUTHOR]

Objectives Mixed-phenotype acute leukemia (MPAL) is a rare disease associated with difficulties in the correct lineage assignment of leukemic cells. One of the least common subtypes within this category is characterized by the simultaneous presence of B- and T-lineage–defining antigens. Each case of suspected B/T MPAL should be considered in light of all available laboratory and clinical data to avoid misdiagnosis. Methods In this study, we describe 6 pediatric patients who presented with leukemic blasts bearing B- and T-lineage antigens at diagnosis, including their clinical, immunophenotypic, morphologic, and cytogenetic characteristics. Results In 3 patients, more or less distinct populations of B- and T-lymphoid origin were found; the other 3 patients had a single mixed-phenotype blast population. All cases fulfilled the World Health Organization criteria, but not all of them turned out to be bona fide cases of B/T MPAL according to the available clinical and laboratory data. Found genetic lesions were helpful for the confirmation of MPAL instead of 2 concomitant tumors, but for a general B/T MPAL diagnosis, genetic studies provided the only descriptive data. Conclusions The accurate diagnosis of B/T MPAL requires a multidisciplinary approach combining high-tech laboratory methods and close cooperation between treating physicians and pathologists. [ABSTRACT FROM AUTHOR]

Introduction: PICALM-MLLT10, formerly CALM-AF10, is a rarely reported fusion gene in hematological malignancies, especially in Asian people.Case presentations: Six patients with PICALM-MALLT10 fusion gene were identified at the First Affiliated Hospital, Zhejiang University School of Medicine, China between October 2019 and October 2023, with a median age of 25 years. Clinical diagnoses included acute myeloid leukemia (AML) in 2 patients, acute lymphoblastic leukemia (ALL) in 3, and mixed phenotype acute leukemia (MPAL) in 1. The prognosis of the patients was poor, and three patients died within 1 year despite of intensive treatment.Conclusion: Patients with PLCALM-MALLT10 can be diagnosed as AML, ALL, MPAL, and other extremely rare hematological malignancies, with mixed clinical manifestations and poor survival. Novel and intensive therapies, including hematopoietic stem cell transplantation, chimeric antigen receptor T-cell immunotherapy, and targeted agents such as the Bcl-2 inhibitor, could be considered in the future.

Objectives: Mixed-phenotype acute leukemia (MPAL) is rare in the clinic, accounting for approximately 2%-5% of acute leukemia cases. Methods: In this study the cohort included 126 patients, of which 125 cases were from re-examined published data and current patients from Shenzhen Longhua District Central Hospital, carrying an ETV6-ABL1 rearrangement from April 15, 2020 to December 19, 2020. The ETS variant transcription factor 6-Abelson proto-oncogene 1 (ETV6-ABL1) fusion gene is mainly seen in malignant hematological diseases such as acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myeloproliferative neoplasms (MPNs). Positivity of both MPAL and ETV6-ABL1 suggest a poor prognosis. This is the first report of B lymphocytic/myeloid mixed-phenotype acute leukemia with ETV6-ABL1 fusion gene positivity. Complete remission was achieved with chemotherapy for lymphoid and myeloid leukemia and targeted therapy with tyrosine kinase inhibitors (TKIs). Results: The level of ETV6-ABL1/ABL decreased from 23.056% to 11.165%. After consolidation chemotherapy, the patient underwent allogeneic hematopoietic stem cell transplantation but died due to intestinal rejection. There are 126 cases of ETV6-ABL1 fusion gene transcript expression in numerous hematologic malignancies reported to date, including 48 cases of ALL, 12 of AML, and 65 of MPN. Eosinophilia is a common characteristic, especially in MPN patients. Conclusion: Survival analysis suggests that the survival time of ALL and MPN patients receiving TKI treatment is better than that of patients not receiving this treatment. Dasatinib or nilotinib, especially the former, is more effective than imatinib for MPN. [ABSTRACT FROM AUTHOR]

Donor cell leukemia (DCL) is a rare complication after allogeneic hematopoietic stem cell transplantation (HSCT) accounting for 0.1% of relapses and presenting as secondary leukemia of donor origin. Distinct in phenotype and cytogenetics from the original leukemia, DCL’s clinical challenge lies in its late onset. Its origin is affected by donor cell anomalies, transplant environment, and additional mutations. A 43-year-old woman, treated for early stage triple-negative breast cancer, developed mixed-phenotype acute leukemia (MPAL), 12 years later. Following induction chemotherapy, myeloablative conditioning, and allo-HSCT from her fully HLA-matched brother, she exhibited multiple cutaneous relapses of the original leukemia, subsequently evolving into DCL of the bone marrow. Cytogenetic analysis revealed a complex male karyotype in 20 out of 21 metaphases, however, still showing the MPAL phenotype. DCL diagnosis was confirmed by 90.5% XY in FISH analysis and the male karyotype. Declining further intensive chemotherapy including a second allo-HSCT, she was subsequently treated with repeated radiotherapy, palliative systemic therapies, and finally venetoclax and navitoclax but died seven months post-DCL diagnosis. This case underlines DCL’s complexity, characterized by unique genetics, further complicating diagnosis. It highlights the need for advanced diagnostic techniques for DCL identification and underscores the urgency for early detection and better prevention and treatment strategies.

Donor cell leukemia (DCL) is a rare complication after allogeneic hematopoietic stem cell transplantation (HSCT) accounting for 0.1% of relapses and presenting as secondary leukemia of donor origin. Distinct in phenotype and cytogenetics from the original leukemia, DCL's clinical challenge lies in its late onset. Its origin is affected by donor cell anomalies, transplant environment, and additional mutations. A 43-year-old woman, treated for early stage triple-negative breast cancer, developed mixed-phenotype acute leukemia (MPAL), 12 years later. Following induction chemotherapy, myeloablative conditioning, and allo-HSCT from her fully HLA-matched brother, she exhibited multiple cutaneous relapses of the original leukemia, subsequently evolving into DCL of the bone marrow. Cytogenetic analysis revealed a complex male karyotype in 20 out of 21 metaphases, however, still showing the MPAL phenotype. DCL diagnosis was confirmed by 90.5% XY in FISH analysis and the male karyotype. Declining further intensive chemotherapy including a second allo-HSCT, she was subsequently treated with repeated radiotherapy, palliative systemic therapies, and finally venetoclax and navitoclax but died seven months post-DCL diagnosis. This case underlines DCL's complexity, characterized by unique genetics, further complicating diagnosis. It highlights the need for advanced diagnostic techniques for DCL identification and underscores the urgency for early detection and better prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Mixed-phenotype acute leukemia (MPAL) is a rare form of leukemia with ambiguous lineage, and there are challenges in accurately diagnosing this entity according to formal criteria. Here we report a case which was initially diagnosed as “AML” based on atypical peripheral blood flow cytometry that was subsequently determined to be B-ALL with KMT2A rearrangement based on marrow results. Although KMT2A rearrangements represent a defining genetic abnormality for acute leukemia of ambiguous lineage, this case did not meet the criteria for MPAL based on WHO 2022 criteria. This case highlights the diagnostic challenges of MPAL and the potential limitations of the current classification. We discuss the most appropriate workup and management of these patients and identify areas for future study.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has cured many patients with malignant hematologic diseases such as mixed phenotype acute leukemia (MPAL), while those relapsing after allo-HSCT still exhibit high mortality, poor prognosis, and no standard treatment modalities. It is necessary to explore more therapeutic modalities for patients with posttransplant relapse to obtain a better prognosis. Case presentation: In this case report, a young male with MPAL received allo- HSCT after reaching complete remission (CR) by induction chemotherapy. Unfortunately, relapse of both myeloid and T lineages occurred nine months later. After receiving demethylating chemotherapy, myeloid lineage measurable residual disease (MRD) turned negative. T-lineage MRD turned negative after CD7-targeted chimeric antigen receptor (CAR)-T cell therapy. The bone marrow remained MRD-negative for 4 months. This case preliminarily demonstrated a long-lasting CR with CD7-targeted CAR-T cell therapy, allowing a better prognosis. Conclusion: Demethylating drugs combined with CD7-targeted CAR-T cell therapy is feasible in treating MPAL patients with relapse after transplantation, with good efficacy and safety, which will be a promising treatment option for MPAL. [ABSTRACT FROM AUTHOR]

Mixed-phenotype acute leukemia (MPAL) is a rare disease. Treatment is often similar to that of acute lymphoblastic leukemia (ALL), but the outcome in adults and the role of allogeneic stem cell transplantation (AlloSCT) are not well defined. We report on 77 adult patients diagnosed with MPAL over the last 10 years and treated with a curative intent. Median age was 49 years; 7.6% of cases had a BCR::ABL1 rearrangement. Thirty patients (39%) were treated with an acute myeloid leukemia (AML)–like induction and 47 (61%) with an ALL-like scheme. The complete remission (CR) rate was 67.6% and an ALL-like therapy was associated with a better CR rate (P = 0.048). The median OS was 41.9 months; age ≤ 60 years was associated with a better OS (67 vs 26 months, P = 0.014). An AlloSCT was performed in 50 patients (65%). The 5-year OS of transplanted patients was 54%. The OS post-AlloSCT was better in patients who were minimal residual disease (MRD)-negative prior to transplant (75.8% vs 45.2%, P = 0.06). This study shows that MPAL patients respond better to an ALL-like induction therapy; that consolidation therapy should include, whenever possible, an AlloSCT and that MRD negativity should be a primary endpoint of treatment. [ABSTRACT FROM AUTHOR]

Mixed-phenotype acute leukemia (MPAL), a rare and heterogeneous category of acute leukemia, is characterized by cross-lineage antigen expression. Leukemic blasts in MPAL can be represented either by one population with multiple markers of different lineages or by several single-lineage populations. In some cases, a major blast population may coexist with a smaller population that has minor immunophenotypic abnormalities and may be missed even by an experienced pathologist. To avoid misdiagnosis, we suggest sorting doubtful populations and leukemic blasts and searching for similar genetic aberrations. Using this approach, we examined questionable monocytic populations in five patients with dominant leukemic populations of B-lymphoblastic origin. Cell populations were isolated either for fluorescence in situ hybridization or for clonality assessment by multiplex PCR or next-generation sequencing. In all cases, monocytic cells shared the same gene rearrangements with dominant leukemic populations, unequivocally confirming the same leukemic origin. This approach is able to identify implicit cases of MPAL and therefore leads to the necessary clinical management for patients. [ABSTRACT FROM AUTHOR]

Mixed-phenotype acute leukemias (MPAL) account for < 4% of all cases of acute leukemias. These are a heterogeneous group of leukemias grouped together by the WHO classification as "rare subtypes." The diagnosis and treatment of MPAL is extremely challenging particularly for low middle income countries. Of these, B/myeloid and T/myeloid combinations are relatively common subtypes. However, megakaryoblastic and erythroid lineages in combination with other lineages are still rare enough to not even be addressed in the WHO classification. To date, there have been only a few reports of mixed B or T cell and megakaryocytic or mixed B or T cell and erythroid leukemias. We report the clinical presentation, diagnostic profile, and disease course of MPAL cases with a biphenotypic pattern consistent with T/megakaryoblastic lineage which is not yet defined in WHO classification. These cases were phenotyped using 8-color flow cytometry (BD FACS CANTO-II) using an extensive panel of markers. Interphase fluorescence in situ hybridization (FISH) was done using dual color dual fusion probes for BCR::ABL1, RUNX1::RUNX1T1, and ETV6::RUNX1, while MLL and CBFB gene rearrangement was tested by break-apart probes. Karyotyping was performed using the conventional GTG-banding technique. Both FISH and karyotyping were analyzed by the automated cell imaging system Leica Biosystems, using Cytovision MB8. The cases presented here satisfy the criteria for both T-lineage assignment (cyCD3 intensity reaches that of normal T-lymphocytes) and acute megakaryoblastic leukemia (≥ 1 megakaryocytic marker in > 50% blasts) and thus represent the first documented examples of this unusual entity from Pakistan. It is crucial to report these cases to gather more data about clinical presentation, diagnostic profile, and disease course. Additionally, the reported cases highlight the limitations of existing classifications which do not address rare subtypes. More importantly, T/megakaryoblastic MPAL needs to be included in the WHO classification as a separate entity. [ABSTRACT FROM AUTHOR]

Mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia (AL), MPAL with BCR::ABL1 fusion is the main subtype of MPAL, mainly affecting adult males. It is an acute leukemia with unique clinical and biological characteristics that involve both the myeloid and lymphatic systems. Gene fusion plays a crucial role in the pathogenesis, diagnosis, prognosis assessment, and treatment of leukemia. We present the first discovery of a novel fusion of RUNX1::STX2 in this subtype, which is co-expressed with BCR::ABL1 fusion. RUNX1 is a crucial transcription factor for hematopoietic differentiation, frequently found to be abnormal in AML, while STX2 may play a role in cancer progression. The RUNX1::STX2 fusion protein may act as the primary negative regulator of wild-type RUNX1, influencing normal cell differentiation and proliferation, consequently elevating the risk of leukemia. The gene fusion status of this patient is unique and complex, requiring further exploration to understand its functional significance in leukemia progression and treatment response., (© 2024 Wiley Periodicals LLC.)

Mixed-phenotype leukemia (MPAL) is a type of acute leukemia in which the blast population shows mixed features of myeloid, T-lymphoid, and/or B-lymphoid differentiation. MPALs are rare and carry a poor prognosis, thus, often pose both a diagnostic and therapeutic challenge. Conventionally, the diagnosis of MPAL requires either a single blast population with a lineage-defining phenotypic expression of multiple lineages (myeloid, B-cell and/or T-cell) (biphenotypic) or two distinct blast populations that each independently satisfy criteria for designation as AML, B-ALL, and/or T-ALL (bilineage). Given the rarity of MPAL, minimal studies have been performed to describe the genomic landscape of these neoplasms. IRB approval was obtained. Central MCC database was searched for any patient with a diagnosis of acute undifferentiated leukemia (AUL), acute leukemia of ambiguous lineage (ALAL), and MPAL. All patient diagnoses were manually reviewed by a hematopathologist to confirm the diagnosis of MPAL. Genomic and molecular data were collated from the EMR and bioinformatically from MCC genomics repositories. Twenty-eight patients with MPAL were identified. Thirteen were female and 15 were male. Average age was 56 years old (range = 28–81). Ten cases were biclonal and 18 were biphenotypic. Diagnoses were as follows: B/myeloid (n = 18), T/myeloid (n = 9), and T/B (n = 1). Cytogenetic analysis (Karyotype +/− FISH) was available for 27 patients. The most frequent recurrent abnormalities were complex karyotype (n = 8), BCR/ABL1 translocation (n = 6), Del 5q/−5 (n = 4), Polysomy 21 (n = 4). Mutational analysis was available for 18 patients wherein mutations were detected in 45 unique genes. The most frequently mutated genes were TP53 (7), RUNX1 (6), WT1 (4), MLL2 (3), FLT3 (3), CBL (2), ASXL1 (2), TET2 (2), MAP3K6 (2), MLL (2), and MAP3K1 (2). Targetable or potentially targetable biomarkers were found in 56% of cases. Overall survival was 19.5 months (range = 0–70 m). Ten patients were treated with an allogeneic stem cell transplant and had superior outcome (p = 0.0013). In one the largest series of MPAL cases to date, we corroborate previous findings with enriched detection of RUNX1 and FLT3–ITD mutations along with discovery of unreported mutations (MAP3K) that may be amenable to therapeutic manipulation. We also report the frequent occurrence of AML with MDS-related changes (AML-MRC)-defining cytogenetic abnormalities (26%). Finally, we show that those patients that received stem cell transplant had a better overall survival. Our findings support the need to genomically profile MPAL cases to exploit opportunities for targeted therapies in this orphan disease with dismal prognosis. [ABSTRACT FROM AUTHOR]

Mixed-phenotype acute leukemia (MPAL) comprises a heterogenous group of leukemias that are genetically, immunophenotypically, and clinically, diverse. Given the rarity of the disease, the diagnosis and treatment of MPAL is extremely challenging. Recent collaborative efforts have made significant progress in understanding the complex genomic landscape of MPAL. Some retrospective studies support starting ALL-type induction followed by an allogeneic stem cell transplant(allo-sct) in the first complete remission; however, due to the inherent bias of retrospective data and small case series, a prospective validation of AML- and ALL-based regimen, and the incorporation of targeted therapies based on genetics and immunophenotype are warranted. The prognosis of adults and children with MPAL varies; this justifies modulating the intensity of therapy, including the use of allo-sct as a consolidation strategy. [ABSTRACT FROM AUTHOR]

Objectives: Classification of acute leukemia involves assigning lineage by resemblance to normal progenitor cells. This approach provides descriptive information about the blast cells that is useful for disease monitoring, provides clues to pathogenesis, and can help clinicians select effective chemotherapeutic regimens. Acute leukemias of ambiguous lineage (ALALs) are those leukemias that either fail to show evidence of myeloid, B-, or T-lymphoid lineage commitment or show evidence of commitment to more than 1 lineage. The different treatment regimens for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) make ALAL a challenge both diagnostically and therapeutically.Methods: Current classification criteria have reduced the reported incidence of mixed-lineage leukemias by emphasizing fewer markers and categorizing some biphenotypic leukemias with recurrent cytogenetic abnormalities as other entities. Several recent studies have explored the genomic and epigenetic landscape of mixed-phenotype acute leukemia (MPAL) and have suggested a further refinement of the World Health Organization classification to emphasize the genomic heterogeneity of MPAL.Results: Genomic and expression profile data for MPAL reveal mutations commonly seen in both AML and ALL, with T-/myeloid MPAL showing overlapping features with early T-cell precursor lymphoblastic leukemia.Conclusions: Our review aimed to discuss the diagnostic challenges, recent genomic studies, and therapeutic strategies in this poorly understood disease. [ABSTRACT FROM AUTHOR]

B/myeloid mixed-phenotype acute leukemia (MPAL) is an uncommon and aggressive leukemia without well-established treatment guidelines and has an inferior outcome. Relapsed/refractory (R/R) acute myeloid leukemia (AML) that is ineligible for aggressive chemotherapy regimens and allogeneic hematopoietic stem-cell transplantation has an extremely poor prognosis. The novel regimen of venetoclax (VEN) combined with hypomethylating agents (HMAs) has a synergistic therapeutic effect and a tolerable safety profile, which has been officially approved by the US Food and Drug Administration (FDA) for newly diagnosed AML in adults who are 75 years or older or patients precluding intensive induction chemotherapy. For R/R and other rare types of AML, no consensus has been reached on the efficacy of VEN-HMA. In addition, there is no available report on treatment-naive B/myeloid MPAL with VEN-HMA. Herein, we present 3 cases of VEN-HMA in treatment-naive B/myeloid MPAL and R/R AML. Its potential efficacy is worthy of further exploration in future researches. [ABSTRACT FROM AUTHOR]

Abstract The translocation PICALM/AF10 is described in multilineage diseases. We report a patient with PICALM/AF10 T/myeloid mixed‐phenotype acute leukemia who achieved durable complete remission after AML‐like treatment suggesting a myeloid origin.

Background: Mixed-phenotype acute leukemia (MPAL) poses a diagnostic and therapeutic dilemma. No consensus exists on the strategy to assign patients with MPAL to either lymphoid- or myeloid-directed treatment. Thus, a better understanding of the characteristics of MPAL is a crucial unmet need. This study aims to provide information on a population-based cohort of children who received treatment based on standard, simple immunophenotypic criteria. Methods: Single-center, retrospective clinical and laboratory reviews of patients with MPAL were provided by morphology, immunophenotyping, cytogenetics, and molecular methods. We identified 242 flow cytometry samples. Of all consecutive pediatric patients with acute leukemia, we identified 8 (3.3%) patients with MPAL fulfilling WHO 2016 criteria; these were classified as follows: B-lymphoid + myeloid (n = 4), T-lymphoid + myeloid (n = 2), and B + T-lymphoid (n = 2). Results: Of 8 MPAL cases, 4 were boys and 4 girls [median age at diagnosis: 10.8 (range 1.1–17) years]. The b3a2 (p210) and e1a2 (p190) BCR/ABL fusion transcripts were detected in 1 patient with B/myeloid MPAL. Regarding the morphology, all patients were initially diagnosed as acute lymphoblastic leukemia, but no morphological characteristics or cytogenetic aberration was particularly predictive of an MPAL. Furthermore, 4 of 8 patients (50%) with MPAL were associated with chromosome 21 monosomy or partial trisomy. Conclusion: Despite no single recurrent chromosomal abnormality that could serve as a hallmark lesion in MPAL, cytogenetic alterations are frequent and predominantly associated with complex karyotype involving chromosome 21 abnormalities.

Mixed-phenotype acute leukemia (MPAL) with BCR::ABL1 fusion is a rare leukemia subtype exhibiting both myeloid and lymphoid traits. Standard treatment involves chemotherapy with a tyrosine kinase inhibitor (TKI). However, establishing the optimal treatment strategy for elderly patients with MPAL with BCR::ABL1 fusion is challenging due to their intolerance to intensive chemotherapy. It has not yet been determined whether therapy with a TKI and prednisolone, a combination known to be effective in elderly patients with B-lymphoblastic leukemia with BCR::ABL1 fusion is also safe and effective for MPAL with BCR::ABL1 fusion. Here we report the first example of an elderly patient with MPAL with BCR::ABL1 fusion who was treated successfully with ponatinib and prednisolone. Despite achieving complete response with dasatinib plus chemotherapy, the patient suffered a relapse during the withdrawal of dasatinib and had two episodes of gastrointestinal bleeding attributed to the dasatinib therapy, necessitating therapy discontinuation. The treatment was then switched to a regimen of ponatinib and prednisolone, and the patient achieved and maintained complete molecular remission for over seven years without any serious adverse events. This case suggests that ponatinib, with or without prednisolone, could be a potential salvage option for elderly patients with MPAL with BCR::ABL1 fusion who suffer relapse or are intolerant to dasatinib., Competing Interests: Conflict of interestNone of the authors have any conflicts of interest to declare., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024, corrected publication 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The histopathological diagnosis of T-lymphoblastic leukemia/lymphoma, NOS (T-ALL), is based on morphology and positivity for CD3 and TdT. Early T-precursor lymphoblastic leukemia/lymphoma (ETP-ALL) and mixed-phenotype acute leukemia (MPAL), T/M, and/or B rarely occur and are usually diagnosed using flow cytometry. Using only formalin-fixed paraffin-embedded tissue raises the risk of misdiagnosis due to underestimation. Immunostaining markers for T cell (CD1a, CD4, CD5, CD8), B cell (CD19, CD10, CD22, CD79a), and stem/myeloid-related cell (CD33, CD34, CD117, MPO, lysozyme) diagnosed 25 T-ALL cases (61%), 7 MPAL (17%), 6 ETP-ALL (15%), and 3 near ETP-ALL (7%), with subsequent analysis of their clinicopathological characteristics. Patients with MPAL had significantly poorer 2-year progression-free survival (14.3% vs. 60.4%, P = 0.012) and 5-year overall survival (28.6% vs. 65.9%, P = 0.011) than did those with T-ALL, whereas ETP-ALL and near ETP-ALL did not. Of the seven patients with MPAL, three were classified as T/B, two as T/M, and two as T/M/B. Because most MPALs (6/7) share the ETP-ALL phenotype, immunohistochemistry for CD19 and MPO should be performed to avoid misdiagnosing MPAL as ETP-ALL. All three patients with TdT-negative MPAL died of the disease. Four patients with MPO-positive MPAL relapsed during the early phase (1-9 months). Five patients received the ALL regimen, but two patients received acute myeloid leukemia and lymphoma regimens, respectively. In this study, MPAL exhibited a poorer prognosis compared to T-ALL, unlike ETP-ALL. Thus, immunohistochemical classification with multiple antibody panels is useful for accurate diagnosis and treatment., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mixed phenotype acute leukemia (MPAL) consists of a leukemia of two different lineages (myeloid, T, and/or B) co-occurring in the same tissue. KMT2A-rearrangement is rare and usually seen in B/myeloid MPAL. We report a unique case of T/myeloid MPAL with a t(v;11q23) KMT2A-rearrangement, with acute myeloid leukemia (AML) in the bone marrow but concurrent T-cell acute lymphoblastic leukemia (T-ALL) in lymph node and skin. Genomic interrogation suggests an undifferentiated stem cells with KMT2A rearrangement as the founder mutation that acquired additional lineage-specific mutations resulting in AML in the marrow and T-ALL in other sites.

BCR-ABL1–positive acute leukemia can be classified into three disease categories: B-lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML), and mixed-phenotype acute leukemia (MPAL). We conducted an integrative analysis of RNA sequencing (RNA-seq) data obtained from 12 BCR-ABL1–positive B-ALL, AML, and MPAL samples to evaluate its diagnostic utility. RNA-seq facilitated the identification of all p190 BCR-ABL1 with accurate splicing sites and a new gene fusion involving MAP2K2. Most of the clinically significant mutations were also identified including single-nucleotide variations, insertions, and deletions. In addition, RNA-seq yielded differential gene expression profile according to the disease category. Therefore, we selected 368 genes differentially expressed between AML and B-ALL and developed two differential diagnosis models based on the gene expression data using 1) scoring algorithm and 2) machine learning. Both models showed an excellent diagnostic accuracy not only for our 12 BCR-ABL1–positive cases but also for 427 public gene expression datasets from acute leukemias regardless of specific genetic aberration. This is the first trial to develop models of differential diagnosis using RNA-seq, especially to evaluate the potential role of machine learning in identifying the disease category of acute leukemia. The integrative analysis of gene expression data by RNA-seq facilitates the accurate differential diagnosis of acute leukemia with successful detection of significant gene fusion and/or mutations, which warrants further investigation.

BCR-ABL1 –positive acute leukemia can be classified into three disease categories: B-lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML), and mixed-phenotype acute leukemia (MPAL). We conducted an integrative analysis of RNA sequencing (RNA-seq) data obtained from 12 BCR-ABL1 –positive B-ALL, AML, and MPAL samples to evaluate its diagnostic utility. RNA-seq facilitated the identification of all p190 BCR-ABL1 with accurate splicing sites and a new gene fusion involving MAP2K2. Most of the clinically significant mutations were also identified including single-nucleotide variations, insertions, and deletions. In addition, RNA-seq yielded differential gene expression profile according to the disease category. Therefore, we selected 368 genes differentially expressed between AML and B-ALL and developed two differential diagnosis models based on the gene expression data using 1) scoring algorithm and 2) machine learning. Both models showed an excellent diagnostic accuracy not only for our 12 BCR-ABL1 –positive cases but also for 427 public gene expression datasets from acute leukemias regardless of specific genetic aberration. This is the first trial to develop models of differential diagnosis using RNA-seq, especially to evaluate the potential role of machine learning in identifying the disease category of acute leukemia. The integrative analysis of gene expression data by RNA-seq facilitates the accurate differential diagnosis of acute leukemia with successful detection of significant gene fusion and/or mutations, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Mixed-phenotype acute leukemia (MPAL) comprises a heterogenous group of leukemias that are genetically, immunophenotypically, and clinically, diverse. Given the rarity of the disease, the diagnosis and treatment of MPAL is extremely challenging. Recent collaborative efforts have made significant progress in understanding the complex genomic landscape of MPAL. Some retrospective studies support starting ALL-type induction followed by an allogeneic stem cell transplant(allo-sct) in the first complete remission; however, due to the inherent bias of retrospective data and small case series, a prospective validation of AML- and ALL-based regimen, and the incorporation of targeted therapies based on genetics and immunophenotype are warranted. The prognosis of adults and children with MPAL varies; this justifies modulating the intensity of therapy, including the use of allo-sct as a consolidation strategy.

To define the fusion genes in T/myeloid mixed-phenotype acute leukemia (T/M MPAL), we performed transcriptome sequencing of diagnostic bone marrow samples from 20 adult patients. Our analysis identified a second instance of a recurrent MED14-HOXA9 chimeric gene resulting from the in-frame fusion of exon 23 of MED14 and exon 1 of HOXA9, the first in an adult patient. The MED14-HOXA9 fusion gene was detected in both the diagnostic and relapsed blasts with reverse transcription-polymerase chain reaction and Sanger sequencing. The patient received combined conventional chemotherapy but suffered relapse at 11 months and died of disease progression one year after the initial diagnosis. Our data suggest that MED14-HOXA9 is a cryptic recurrent aberration in T/M MPAL, which might indicate an aggressive clinical course and inferior outcome after conventional chemotherapy. Further studies will be carried out to reveal the effects of the MED14-HOXA9 fusion on the differentiation and proliferation of leukemia stem cells, as well as suitable treatment strategies for this emerging entity.

To define the fusion genes in T/myeloid mixed-phenotype acute leukemia (T/M MPAL), we performed transcriptome sequencing of diagnostic bone marrow samples from 20 adult patients. Our analysis identified a second instance of a recurrent MED14-HOXA9 chimeric gene resulting from the in-frame fusion of exon 23 of MED14 and exon 1 of HOXA9 , the first in an adult patient. The MED14-HOXA9 fusion gene was detected in both the diagnostic and relapsed blasts with reverse transcription-polymerase chain reaction and Sanger sequencing. The patient received combined conventional chemotherapy but suffered relapse at 11 months and died of disease progression one year after the initial diagnosis. Our data suggest that MED14-HOXA9 is a cryptic recurrent aberration in T/M MPAL, which might indicate an aggressive clinical course and inferior outcome after conventional chemotherapy. Further studies will be carried out to reveal the effects of the MED14-HOXA9 fusion on the differentiation and proliferation of leukemia stem cells, as well as suitable treatment strategies for this emerging entity. [ABSTRACT FROM AUTHOR]

The translocation PICALM/AF10 is described in multilineage diseases. We report a patient with PICALM/AF10 T/myeloid mixed‐phenotype acute leukemia who achieved durable complete remission after AML‐like treatment suggesting a myeloid origin. [ABSTRACT FROM AUTHOR]

Objectives: Mixed-phenotype acute leukemia (MPAL) is rare in the clinic, accounting for approximately 2%-5% of acute leukemia cases., Methods: In this study the cohort included 126 patients, of which 125 cases were from re-examined published data and current patients from Shenzhen Longhua District Central Hospital, carrying an ETV6-ABL1 rearrangement from April 15, 2020 to December 19, 2020. The ETS variant transcription factor 6-Abelson proto-oncogene 1 (ETV6-ABL1) fusion gene is mainly seen in malignant hematological diseases such as acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myeloproliferative neoplasms (MPNs). Positivity of both MPAL and ETV6-ABL1 suggest a poor prognosis. This is the first report of B lymphocytic/myeloid mixed-phenotype acute leukemia with ETV6-ABL1 fusion gene positivity. Complete remission was achieved with chemotherapy for lymphoid and myeloid leukemia and targeted therapy with tyrosine kinase inhibitors (TKIs)., Results: The level of ETV6-ABL1/ABL decreased from 23.056% to 11.165%. After consolidation chemotherapy, the patient underwent allogeneic hematopoietic stem cell transplantation but died due to intestinal rejection. There are 126 cases of ETV6-ABL1 fusion gene transcript expression in numerous hematologic malignancies reported to date, including 48 cases of ALL, 12 of AML, and 65 of MPN. Eosinophilia is a common characteristic, especially in MPN patients., Conclusion: Survival analysis suggests that the survival time of ALL and MPN patients receiving TKI treatment is better than that of patients not receiving this treatment. Dasatinib or nilotinib, especially the former, is more effective than imatinib for MPN., Competing Interests: Conflicts of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Mixed-phenotype acute leukemia (MPAL) with FLT3 -TKD mutations is a rare and challenging subtype of leukemia. Effective management strategies are crucial for improving patient outcomes. A 31-year-old man with FLT3 -TKD-mutated MPAL achieved hematological remission through the JALSG ALL202-O protocol and gilteritinib, followed by cord blood transplantation (CBT). Post-transplant complications included adenovirus-induced hemorrhagic cystitis, managed with bladder irrigation and ribavirin, and engraftment failure, necessitating a second CBT on Day 35. Subsequent adenoviral conjunctivitis resolved with vidarabine. The patient achieved neutrophil engraftment by Day 76 and was discharged on Day 173 without relapse. This case highlights the importance of vigilant supportive care and tailored therapy in managing MPAL with FLT3 mutations, especially in the context of post-transplant complications., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Mixed-phenotype acute leukemia (MPAL) is a rare form of leukemia with ambiguous lineage, and there are challenges in accurately diagnosing this entity according to formal criteria. Here we report a case which was initially diagnosed as "AML" based on atypical peripheral blood flow cytometry that was subsequently determined to be B-ALL with KMT2A rearrangement based on marrow results. Although KMT2A rearrangements represent a defining genetic abnormality for acute leukemia of ambiguous lineage, this case did not meet the criteria for MPAL based on WHO 2022 criteria. This case highlights the diagnostic challenges of MPAL and the potential limitations of the current classification. We discuss the most appropriate workup and management of these patients and identify areas for future study., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Mixed-phenotype acute leukemia (MPAL) poses a diagnostic and therapeutic dilemma. No consensus exists on the strategy to assign patients with MPAL to either lymphoid- or myeloid-directed treatment. Thus, a better understanding of the characteristics of MPAL is a crucial unmet need. This study aims to provide information on a population-based cohort of children who received treatment based on standard, simple immunophenotypic criteria. Single-center, retrospective clinical and laboratory reviews of patients with MPAL were provided by morphology, immunophenotyping, cytogenetics, and molecular methods. We identified 242 flow cytometry samples. Of all consecutive pediatric patients with acute leukemia, we identified 8 (3.3%) patients with MPAL fulfilling WHO 2016 criteria; these were classified as follows: B-lymphoid + myeloid (n = 4), T-lymphoid + myeloid (n = 2), and B + T-lymphoid (n = 2). Of 8 MPAL cases, 4 were boys and 4 girls [median age at diagnosis: 10.8 (range 1.1–17) years]. The b3a2 (p210) and e1a2 (p190) BCR/ABL fusion transcripts were detected in 1 patient with B/myeloid MPAL. Regarding the morphology, all patients were initially diagnosed as acute lymphoblastic leukemia, but no morphological characteristics or cytogenetic aberration was particularly predictive of an MPAL. Furthermore, 4 of 8 patients (50%) with MPAL were associated with chromosome 21 monosomy or partial trisomy. Despite no single recurrent chromosomal abnormality that could serve as a hallmark lesion in MPAL, cytogenetic alterations are frequent and predominantly associated with complex karyotype involving chromosome 21 abnormalities. [ABSTRACT FROM AUTHOR]

Background: Optimal chemotherapy for treating mixed-phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain uncertain. Major limitations in interpreting available data are MPAL's rarity and the use of definitions other than the currently widely accepted criteria: the World Health Organization 2016 (WHO2016) classification.Methods: To assess the relative efficacy of chemotherapy types for treating pediatric MPAL, the Children's Oncology Group (COG) Acute Leukemia of Ambiguous Lineage Task Force assembled a retrospective cohort of centrally reviewed WHO2016 MPAL cases selected from banking studies for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Patients were not treated in COG trials; treatment and outcome data were captured separately. The findings were then integrated with the available, mixed literature to develop a prospective trial in pediatric MPAL.Results: The central review confirmed that 54 of 70 cases fulfilled WHO2016 criteria for MPAL. ALL induction regimens achieved remission in 72% of the cases (28 of 39), whereas AML regimens achieved remission in 69% (9 of 13). The 5-year event-free survival (EFS) and overall survival (OS) rates for the entire cohort were 72% ± 8% and 77% ± 7%, respectively. EFS and OS were 75% ± 13% and 84% ± 11%, respectively, for those receiving ALL chemotherapy alone without HSCT (n = 21).Conclusions: The results of the COG MPAL cohort and a literature review suggest that ALL chemotherapy without HSCT may be the preferred initial therapy. A prospective trial within the COG is proposed to investigate this approach; AML chemotherapy and/or HSCT will be reserved for those with treatment failure as assessed by minimal residual disease. Embedded biology studies will provide further insight into MPAL genomics. [ABSTRACT FROM AUTHOR]

Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of hematopoietic malignancies in which blasts show markers of multiple developmental lineages and cannot be clearly classified as acute myeloid or lymphoblastic leukemias. Historically, various names and classifications were used for this rare entity accounting for 2-5% of all acute leukemias depending on the diagnostic criterias used. The currently valid classification of myeloid neoplasms and acute leukemia published by the World Health Organization (WHO) in 2016 refers to this group of diseases as MPAL. Because adverse cytogenetic abnormalities are frequently present, MPAL is generally considered a disease with a poor prognosis. Knowledge of its treatment is limited to retrospective analyses of small patient cohorts. So far, no treatment recommendations verified by prospective studies have been published. The reported data suggest that induction therapy for acute lymphoblastic leukemia followed by allogeneic hematopoietic cell transplantation is more effective than induction therapy for acute myeloid leukemia or consolidation chemotherapy. The establishment of cooperative groups and international registries based on the recent WHO criterias are required to ensure further progress in understanding and treatment of MPAL. This review summarizes current knowledge on the diagnosis, classification, prognosis and treatment of MPAL patients.

Background: Biphenotypic acute leukemia (BAL), or mixed-phenotype acute leukemia (MPAL) represents a rare subgroup of acute leukemia which co-expresses markers for either more than one lineage in a homogenous blast population or the coexistence of two blast populations of different lineages. Proper diagnosis and classification of BAL are extremely important for patients' outcome since BAL usually has a poor prognosis. Purpose: The objective of this study was to identify the incidence of biphenotypic acute leukemia, their clinical characteristics and outcome of BAL patients with the chemotherapy treatment and Hematopoietic Stem Cell Transplantation (HSCT) after initial complete remission. Patients and methods: Ten cases of biphenotypic acute leukemia were analyzed for their clinical characteristics, immunological phenotypes, chemotherapy methods for induction initial complete remission and outcome data, including induction chemotherapy, complete remission (CR) and the overall survival time, relapse and death. This study was an observational, retrospective, and descriptive study of the clinical aspects of BAL. Cytogenetics and fusion genes analysis were also done with bone marrow samples using G-banding analysis and karyotyped according to the International System for Human Cytogenetic Nomenclature. The fusion genes' mutational status was determined by real-time PCR (RT-PCR). Gene mutation analyses were conducted with next-generation sequencing method. Results: Among 10 BAL patients, 4 cases carried B/Myeloid phenotype, 4 cases carried T/Myeloid phenotype and 2 cases carried T/B phenotype. Cytogenetic analysis showed that 3 of the 10 cases had clonal abnormalities. Of the four cases of fusion gene aberration, two patients had RUNX1 gene mutation, one patient had BCR/ABL fusion gene mutation, and one patient had JAK1, JAK3, FBXW7 mutation. Overall, 5 of 8 (62.5%) BAL patients with chemotherapy achieved complete remission (CR) after their initial induction therapy. In the AML-directed therapy group, 1 of 2 (50%) patients achieved CR. Meanwhile, 4 of 6 (66.7%) patients achieved CR after ALL-directed induction chemotherapy. Two patients received Hematopoietic Stem Cell Transplantation (HSCT) after initial CRs, one patient died two months after transplantation due to pulmonary infection, and another patient is still alive. With an average of 14.3 (4.0–42.0) months' follow-ups, the median survival time was 7 months. Although patients achieved CR after initial chemotherapy, the relapse rate was very high and the CR rate after relapse was very low. Conclusion: Our results confirmed that BAL is a rare malignancy with a very poor prognosis. Patients with ALL-directed chemotherapy achieved a better CR rate compared to those with AML-directed chemotherapy. Patients should receive HSCT after initial CR whenever it is possible. [ABSTRACT FROM AUTHOR]

Mixed-phenotype acute leukemia (MPAL) is the infrequent type of acute leukemia characterized by immunophenotypic and/or cytochemical features of both lineages, but the diagnosis of this disease still is a challenge. In this study, we analyzed immunophenotyping, cytochemistry and frequency of MPAL patients to better diagnosis of MPAL characteristics according to WHO 2016 criteria for the first time in Iran. In this retrospective study, 27 patients were diagnosed as MPAL based on WHO 2016 criteria during 2014-2017. Flow cytometric immunophenotyping was performed on PB and BM samples evaluation of different CD marker expressions in MPAL subsets. RT-PCR was performed for the analyses of BCR/ABL1 fusion in MPAL subsets. Among 27 cases, (70.4%) 19 cases were B + My, (22.22%) 6 cases were T + My, and 2 cases (7.40%) were B + T + My. CD34, CD19, HLA-DR, TdT, CD22, iMPO were positive in majority of B + My cases. CD45, iMPO, iCD3, CD7, CD2 and CD5 were positive in majority of T + My cases. HLA-DR, TdT, CD10, CD22, iCD79a, iMPO, CD45, iCD3, CD7, CD3, CD2, CD5 were positive in majority of B + T + My cases. BCR/ABL1 fusion was positive for 3 cases (11.1%) of p190 fusion and 2 cases (7.4%) of p210 fusion in B + My cases. WHO 2016 criteria are the current standard for diagnosing MPAL. Also, evaluation of TdT, CD2, CD5, CD7 expressions by flow cytometry in EGIL criteria is useful for the better diagnosis of MPAL subsets. In addition, evaluation of BCR/ABL1 and MLL rearrangements in patients should be part of standard work-up in MPAL. [ABSTRACT FROM AUTHOR]

Leukemia is characterized by the uncontrolled production of leukemic cells and impaired normal hematopoiesis. Although the combination of chemotherapies and hematopoietic stem cell transplantation has significantly improved the outcome of leukemia patients, a proportion of patients still suffer from relapse after treatment. Upon relapse, a phenomenon termed “lineage switch” is observed in a subset of leukemia patients, in which conversion of lymphoblastic leukemia to myeloid leukemia or vice versa is observed. A rare entity of leukemia called mixed-phenotype acute leukemia exhibits co-expression of markers representing two or three lineages. These two phenotypes regarding the lineage ambiguity suggest that the fate of some leukemia retain or acquire a certain degree of plasticity. Studies using animal models provide insight into how lineage specifying transcription factors can enforce or convert a fate in hematopoietic cells. Modeling lineage conversion in normal hematopoietic progenitor cells may improve our current understanding of how lineage switch occurs in leukemia. In this review, we will summarize the role of transcription factors and microenvironmental signals that confer fate plasticity to normal hematopoietic progenitor cells, and their potential to regulate lineage switching in leukemias. Future efforts to uncover the mechanisms contributing to lineage conversion in both normal hematopoiesis and leukemia may pave the way to improve current therapeutic strategies.

Objectives: Philadelphia chromosome-like (Ph-like) genetic alterations define a subset of B lymphoblastic leukemia/lymphoma (B-ALL), which represents a separate provisional entity in the World Health Organization 2016 updated classification. However, these alterations have not been described outside the context of B-ALL. Methods: Cytogenomic array and molecular analysis identified a Ph-like signature in a mixed-phenotype acute leukemia (MPAL), B/myeloid, confirmed using conventional immunophenotypic and cytochemical analysis. Results: Flow cytometry identified a blast population demonstrating a B-cell lineage and myeloperoxidase positivity. A P2RY8-CRLF2 fusion and JAK1 mutation were detected, both of which are associated with Ph-like features. Conclusions: To our knowledge, this is the first report of Ph-like MPAL, which may represent a new diagnostic entity. We emphasize the need for refinement of diagnostic criteria for MPALs and highlight an opportunity for expansion of inclusion criteria in ongoing clinical trials studying the use of tyrosine kinase inhibitor therapy to include cases of Ph-like MPAL. [ABSTRACT FROM AUTHOR]

Bilineage T lymphoid and myeloid (T/My) neoplasms are rare entities among the hematopoietic and lymphoid malignancies. The majority of patients present with leukemic symptoms in which blasts are observed in the peripheral blood (PB) or bone marrow (BM) at a percentage of >20% of nucleated cells. Only a minimal number of cases of T/My bilineage hematopoietic and lymphoid malignancy have been reported with extramedullary infiltration as the initial symptom. The origin of the neoplastic cells in T/My bilineage malignancy has been documented as the hematopoietic stem cells. The present study reports the case of a 31‑year‑old man with a T/My bilineage malignancy, which initially showed cervical lymph node enlargement beyond the diagnostic criteria of leukemia in the PB and in the BM. Two distinct malignant populations were detected in the cervical lymph node and pleural effusion, one of which was positive for MPO‑staining, while the other was positive for cytoplasmic cluster of differentiation 3. Mutations in platelet‑derived growth factor receptor α, platelet‑derived growth factor receptor β, fibroblast growth factor receptor 1 and other chromosome abnormalities were excluded. The patient obtained complete remission after conventional chemotherapy, but relapsed with bilineage leukemia within a short period of time. Lymphoid and myeloid lineages have been reported to be differentiated from multipotent progenitors asymmetrically. However, the cellular mutation stage in T/My bilineage malignancy remains unclear. The present study also reviews the origin, development and therapeutic strategies for extramedullary T/My bilineage malignancy. [ABSTRACT FROM AUTHOR]

Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of hematopoietic malignancies in which blasts show markers of multiple developmental lineages and cannot be clearly classified as acute myeloid or lymphoblastic leukemias. Historically, various names and classifications were used for this rare entity accounting for 2-5% of all acute leukemias depending on the diagnostic criterias used. The currently valid classification of myeloid neoplasms and acute leukemia published by the World Health Organization (WHO) in 2016 refers to this group of diseases as MPAL. Because adverse cytogenetic abnormalities are frequently present, MPAL is generally considered a disease with a poor prognosis. Knowledge of its treatment is limited to retrospective analyses of small patient cohorts. So far, no treatment recommendations verified by prospective studies have been published. The reported data suggest that induction therapy for acute lymphoblastic leukemia followed by allogeneic hematopoietic cell transplantation is more effective than induction therapy for acute myeloid leukemia or consolidation chemotherapy. The establishment of cooperative groups and international registries based on the recent WHO criterias are required to ensure further progress in understanding and treatment of MPAL. This review summarizes current knowledge on the diagnosis, classification, prognosis and treatment of MPAL patients. [ABSTRACT FROM AUTHOR]

Objectives: Diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) requires immunophenotypic evidence of B-lineage and absence of specific myeloid or T-lineage markers. Rare cases of otherwise typical B-ALL express myeloperoxidase (MPO) detectable by flow cytometry with an absence of other myeloid markers, but the clinical significance of this finding is not well studied.Methods: A retrospective cohort analysis of flow cytometry and clinical data was performed to investigate the clinical outcome of this specific group of patients.Results: Twenty-nine cases of otherwise typical B-ALL that expressed MPO by flow cytometry (B-ALL-isoMPO) without expression of other myeloid markers were identified. The B-ALL-isoMPO group had a significantly increased incidence of relapse (univariate log rank P  = .0083; multivariate hazard ratio, 2.50; 95% confidence interval, 1.07-5.85; P  = .034) and significantly worse event-free survival by univariate analysis (log rank P  = .0066) compared with a reference group of patients with B-ALL from the same time period (n = 264).Conclusions: To our knowledge, this is the first report to document the clinical outcomes in a group of pediatric patients with B-ALL that expresses MPO in the absence of other myeloid markers. This group had an increased rate of relapse and a worse event-free survival than the patients with B-ALL who did not express MPO. [ABSTRACT FROM AUTHOR]

The correct classification of acute leukemias (AL) is an essential part in the evaluation of any patient with this disease. Historically, CD117 has been an important asset in the diagnosis of patients with mixed-phenotype acute leukemia (MPAL). In an attempt to simplify the diagnosis of MPAL with fewer and more lineage specific markers, the World Health Organization (WHO) proposed in 2008 a new criteria for the diagnosis of this type of AL, which excluded CD117 from the myeloid markers that are utilized to diagnose MPAL. In order to assess whether CD117 is necessary in the diagnosis of MPAL, we evaluated the sensitivity and specificity of CD117 for acute myeloid leukemia (AML) in 331 patients with AL. The calculated sensitivity of CD117 for AML was 85.88% (103/120), while the specificity was 83.9% (177/211). Besides myeloperoxidase (MPO), which was used as the gold standard in differentiating AML from other type of ALs, the most specific markers for AML in our study were CD14 and CD64 (99.5 and 95.6%). Although the specificity of CD117 in this study is not as high as CD14 and CD64, markers concomitantly used in this this study and in the WHO classification, based on the results of other researches (i.e. the specificity of CD117 for AML was 100% in one study) and due to the fact that its specificity for AML in this study is relatively high, we recommend the use CD117 in assigning a myeloid lineage in MPAL. [ABSTRACT FROM AUTHOR]