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A 12-year-old female domestic short-haired cat was presented due to weight loss, anorexia, and tachypnea. Complete blood count revealed severe anemia, leukocytosis with massive undifferentiated blast cells, and thrombocytopenia. Bone marrow aspiration showed acute myeloid leukemia, subclassified as monoblastic leukemia (M5a) based on the outcomes of the cytochemistry examinations. The SNAP feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) test using whole blood was negative. In addition, FeLV/FIV proviral polymerase chain reaction test using bone marrow aspirate was also negative. Although the cat was treated with doxorubicin, cytosine arabinoside, and prednisolone, anemia did not improve without blood transfusion. The owner declined further treatment after 2 months, and the cat died a few days later.

Background: Chronic lymphocytic leukemia (CLL) is associated with an increased risk of other malignancies, such as skin and. second hematological malignancies. In the majority of cases, this usually involves a disease transformation to an aggressive non-Hodgkin lymphoma, multiple myeloma or prolymphocytic lymphoma. CLL patients can rarely develop acute myeloid leukemia (AML). We have reported a case in which there was simultaneous presentation of AML and CLL. Case report: A 78-year-old man presented with tiredness and mucosal bleeding. Laboratory evaluation revealed a white blood count of 220,970 μ/l with 4% of blasts,69% lymphocytes and 20% monocytes, hemoglobin of 6.7 g/dl, platelet count of 29,000 μ/l. A bone marrow aspirate revealed markedly hypercellular bone marrow with 21% blasts and promonocytes and 47% mature lymphocytes. A peripheral blood flow cytometry demonstrated a mature CD5 and CD23 positive B-cell population expressing CD19, low-density CD 20, CD11c, CD25, CD81, CD39 and lambda light chains at 53.02% of lymphocytes, consistent with B-CLL.; In addition, a second population showed CD33, CD13 low-density, CD11b, CD64, CD14, CD36, HLA-DR, CD56, CD123, CD11c, CD38 and CD9 positives in 39.35% of immature monocytes, consistent with acute monoblastic leukemia. Cytogenetics on bone marrow aspirate showed 48,XY, +4,+8[18] / 46,XY [2]. Conclusion: The present report highlights the rare possibility of the development of a myeloid malignancy in a patient with lymphoid malignancy. Most of these cases more frequently present as a secondary event in patients receiving chemotherapeutic agents for CLL.Knowledge of this rare association is the key to timely and accurate diagnosis, particularly in patients with atypical presentation. Existing literature demonstrates that AML may also develop concurrently or even after the diagnosis of treatment-naïve CLL patients. Further studies of such patients have potential to provide insight into the pathogenesis of myeloid as well as lymphoid malignancies.

The intestine‐specific caudal‐related homeobox gene‐2 (CDX2) homeobox gene, while being a tumor suppressor in the gut, is ectopically expressed in a large proportion of acute leukemia and is associated with poor prognosis. Here, we report that turning on human CDX2 expression in the hematopoietic lineage of mice induces acute monoblastic leukemia, characterized by the decrease in erythroid and lymphoid cells at the benefit of immature monocytic and granulocytic cells. One of the highly stimulated genes in leukemic bone marrow cells was BMP and activin membrane‐bound inhibitor (Bambi), an inhibitor of transforming growth factor‐β (TGF‐β) signaling. The CDX2 protein was shown to bind to and activate the transcription of the human BAMBI promoter. Moreover, in a leukemic cell line established from CDX2‐expressing mice, reducing the levels of CDX2 or Bambi stimulated the TGF‐β‐dependent expression of Cd11b, a marker of monocyte maturation. Taken together, this work demonstrates the strong oncogenic potential of the homeobox gene CDX2 in the hematopoietic lineage, in contrast with its physiological tumor suppressor activity exerted in the gut. It also reveals, through BAMBI and TGF‐β signaling, the involvement of CDX2 in the perturbation of the interactions between leukemia cells and their microenvironment., Abnormal expression of the homeodomain transcription factor caudal‐related homeobox gene‐2 (CDX2) is associated with poor prognosis of leukemia patients. Here, we report that turning on human CDX2 expression in the hematopoietic lineage of mice induces acute monoblastic leukemia, through inhibition of the lymphocytic lineage and accumulation of immature monoblasts mediated by the stimulation of the BMP and activin membrane‐bound inhibitor that blocked transforming growth factor‐β‐dependent differentiation of monocytes.

Background Langerhans cell tumors are rare clonal disorders characterized by neoplastic proliferation of dendritic cells that can be further classified into the subtypes Langerhans cell histiocytosis and Langerhans cell sarcoma, which are rare neoplasms exhibiting aggressive features and a poor prognosis. In addition to illustrating the refractoriness and poor outcomes of multisystem Langerhans cell histiocytosis in adults, specific events in this case highlight important characteristics of disease biology that warrant detailed discussion and exposition to a wider audience. Case presentation We describe the case of a 42-year-old Caucasian man with Langerhans cell histiocytosis diagnosed from a lesion on the left arm that presented with constitutional symptoms, early satiety, and weight loss. Esophagogastroduodenoscopy showed extensive esophageal and duodenal involvement by Langerhans cell histiocytosis with features of Langerhans cell sarcoma. He was initially treated for Langerhans cell histiocytosis with low doses of cytarabine until he eventually presented clear transformation to acute monoblastic leukemia with complex karyotype that could not be properly controlled, leading eventually to death. Conclusions Langerhans cell histiocytosis remains an exceedingly rare entity in adults, frequently presenting as multisystem disease with risk organ involvement. Langerhans cell sarcoma represents an aggressive subtype with extremely poor prognosis for which intensive acute myeloid leukemia induction should be strongly considered.

Key Clinical Message t(11;17) is a rare but recognized finding usually found in Acute Promyelocytic Leukemia with variant RARA translocation (APLv). We present a case of Acute Myeloid Leukemia with t(11;17) that has different break points than those occurring in APLv. The diagnosis of acute myeloid leukemia, not otherwise specified, acute monoblastic leukemia was reached after a thorough investigation. Reaching the correct diagnosis and distinguishing these two entities are essential as they have different management, prognosis, and overall survival.

Sweet's syndrome (SS), also known as acute febrile neutrophilic dermatosis is often associated with a hematological malignancy, especially acute myeloid leukemia (AML) and myeloid dysplasia syndrome. Histopathologically, SS is characterized by diffuse infiltrates in the upper dermis, predominantly consisting of mature neutrophils. The origin of neutrophils invading the skin remains unknown. Herein, we report a patient with concurrent acute monoblastic leukemia and SS who initially presented with discrete erythematous papules and nodules on the neck. Single nucleotide polymorphism (SNP) array and next generation sequencing (NGS) revealed a concordant fms-related tyrosine kinase-3 (FLT-3) gene mutation in the bone marrow and skin lesion, indicating that the neutrophilic infiltrates were clonally related to the underlying myeloid neoplasm. This is the first case report of concurrent SS and AML, in which SNP array and NGS analysis were applied to confirm the clonality of the neutrophilic infiltrates.

In acute myeloid leukemia (AML), patients may harbor pre-leukemic hematopoietic stem cells (HSCs) containing some, but not all, of the mutations observed in the leukemic cells. These pre-leukemic HSCs may survive induction chemotherapy and contribute to AML relapse by obtaining additional mutations. We report here an acute monoblastic leukemia (AMoL) patient who later developed an unclassifiable myeloproliferative neoplasm (MPN-U). Whole-exome sequencing and cluster analysis demonstrated the presence of three distinct major clones during the clinical course: (1) an AMoL clone with ASXL1, CBL, and NPM1 somatic mutations, likely associated with the pathogenesis, and GATA2, SRSF2, and TET2 mutations, (2) an AMoL remission clone, with mutated GATA2, SRSF2, and TET2 only (possibly the founding clone (pre-leukemic HSC) that survived chemotherapy), (3) a small subclone which had JAK2 mutation during the AMoL remission, appearing at MPN-U manifestation with additional mutations. These findings suggest that pre-leukemic HSCs in AML patients may give rise to non-AML myeloid malignancies. This is the first report to analyze the clonal evolution from AMoL to MPN-U, which may provide new insight into the development of myeloid malignancies.

Disseminated intravascular coagulation (DIC) is usually observed in acute promielocytic leukemia (AML-M3). DIC is diagnosed in other types of acute myeloid leukemia less frequently, but among them, the largest percentage applies to patients with acute monoblastic leukemia (AML-M5), with the release of procoagulation substances and cytokines from blasts. Laboratory and clinical symptoms of DIC appeared at the time of diagnosis of leukemia or just after initiation of induction treatment. We present two children with AML-M5 and rearrangement of the MLL gene, treated according to BFM AML 98 Interimphase 2004 and BFM AML 2012 protocol. The first patient had laboratory signs of DIC as undetectable (below quantifiable levels of) coagulation parameters without any clinical symptoms diagnosed at the same time as leukemia and persistent during the induction chemotherapy. The second patient had changes first in the coagulogram on the second day of induction chemotherapy. In the subsequent days, major bleeding from mucous membranes of the oral cavity, requiring intensive substitute treatment, was observed. The highest concentration of D-dimers with the lowest concentration of fibrinogen was observed on day 5 of chemotherapy in both the cases. Coagulation parameters were within normal levels on the last day, e.g. on Day 8 of induction chemotherapy, despite intensive substitution therapy.

Armillaridin (AM) is an aromatic ester compound isolated from Armillaria mellea. Treatment with AM markedly reduced the viability of human chronic myelogenous leukemia K562, chronic erythroleukemia HEL 92.1.7, and acute monoblastic leukemia U937 cells, but not normal human monocytes, in a dose- and time-dependent manner. Treatment of K562 cells with AM caused changes characteristic of autophagy. Only a small amount of AM-treated K562 cells exhibited apoptosis. By contrast, AM treatment resulted in extensive apoptotic features in U937 and HEL 92.1.7 cells without evident autophagy. The autophagy of K562 cells induced by AM involved autophagic flux, including autophagosome induction, the processing of autophagosome-lysosome fusion and downregulation of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3). By bcr-abl knockdown, the growth inhibition of K562 cells caused by AM was partially blocked, suggesting that AM-induced cell death might be a bcr-abl-dependent mode of autophagy-associated cell death. In conclusion, AM is capable of inhibiting growth and inducing autophagy-associated cell death in K562 cells, but not in normal monocytes. It may have potential to be developed as a novel therapeutic agent against leukemia.

Bone Marrow Necrosis in Acute Monoblastic Leukemia A 56-year-old man presented with fever and shortness of breath. The white-cell count was 142,000 per microliter, and a diagnosis of acute monoblas...

A 70-year-old female was referred for brown-to-gray colored papules and nodules on her lower legs. She had been diagnosed with diffuse large B-cell lymphoma (DLBCL) in her stomach, and myelodysplastic syndrome (MDS) by bone marrow biopsy. Three years after complete remission of DLBCL, she experienced DLBCL recurrence in her small bowel and was hospitalized. MDS had been stationary, but during the treatment of DLBCL, her laboratory findings suggested signs of leukemia. Bone marrow biopsy was done, and acute monoblastic leukemia (AMoL) was diagnosed. After 1 cycle of chemotherapy for AMoL, skin lesions developed, and her skin biopsy showed cutaneous T-cell lymphoma (CTCL). Terminal deoxynucleotidyl transferase staining and CD123 staining were negative, and bone marrow re-biopsy conducted after the skin lesion developed still showed monoblastic proliferation. Whether the CTCL represented with an AMoL lineage switch could not be completely proved due to the absence of molecular or clonal marker evaluations, but the possibility of coexistence of three different malignancies was higher. During treatment, a neutropenic fever developed, and the patient died due to sepsis. We herein report a rare case of CTCL accompanied by AmoL and DLBCL.

We report a case of a 47-year-old male from West Africa who presented with sepsis and was found to have acute monoblastic leukemia associated with tetrasomy 8 detected on bone marrow samples. This was the only chromosomal abnormality found. Tetrasomy 8 is a rare genetic finding that has been reported in acute myeloid leukemia (AML), predominantly the monocytic lineage. It carries a poor prognosis with a high mortality rate.

Acute monoblastic leukemia (AMoL) is a rare hematopoietic neoplasm, and simultaneous occurrence of acute monoblastic leukemia with chronic lymphocytic leukemia is very rare and only a few cases have been reported in the literature. We here report a rare case of dual hematological malignancy in an 85-year-old male. The peripheral blood and bone marrow examination revealed dual population of atypical cells, comprising large cells with opened-up chromatin having monocytic appearance and small mature-appearing lymphocytes. Flowcytometric immunophenotyping confirmed the monocytic lineage of cells, whereas small lymphocytes showed the immunophenotype consistent with chronic lymphocytic leukemia (CLL). The final diagnosis was made as acute monoblastic leukemia with associated CLL. This is a rare case scenario, and this highlights the importance of careful morphological examination and flowcytometric immunophenotyping in the exact characterization of hematopoietic malignancies.

Introduction. Invasive fungal infection is among the leading causes of morbidity, mortality, and economic burden for patients with acute leukemia after induction of chemotherapy. In the past few decades, the incidence of invasive fungal infection has increased dramatically. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. Mucorales). Neutropenic patients are at a high risk of developing an invasive mucormycosis with fulminant course and high mortality rate (35-100%). Case Outline. We are presenting the case of a 72-year-old male with an acute monoblastic leukemia. The patient was treated during five days with hydroxycarbamide 2 × 500 mg/day, followed by cytarabine 2 × 20 mg/sc over the next 10 days. He developed febrile neutropenia, headache, and edema of the right orbital region of the face. Computed tomography of the sinuses revealed shadow in sinuses with thickening of mucosa of the right paranasal sinuses. Lavage and aspirate from the sinuses revealed Rhizopus oryzae. Mucormycosis was successfully treated with amphotericin B (5 mg/kg/day) followed by ketoconazole (400 mg/day). Two months later the patient died from primary disease. Conclusion. In patients with acute leukemia who developed aplasia, febrile neutropenia, and pain in paranasal sinuses, fungal infection should be taken into consideration. New and non-invasive methods for taking samples from sinuses should be standardized in order to establish an early and accurate diagnosis of mucormycosis with the source in paranasal sinuses, and to start early treatment by a proper antifungal drug. Clear communication between physician and mycologist is critical to ensure proper and timely sampling of lavage and aspirate from sinuses and correct specimen processing when mucormycosis is suspected clinically. [Projekat Ministartsva nauke Republike Srbije, br. OI 175034]

We report a case of acute myeloid leukemia (AML) with two cytogenetically unrelated clones. The patient was a 45-year-old male who was diagnosed with acute monoblastic leukemia (AMoL). Initial G-band analysis showed 51,XY,+6,+8,inv(9)(p12q13)c,+11,+13,+19[12]/52,idem,+Y[8], but G-band analysis after induction therapy showed 45,XY,-7,inv(9)(p12q13)c[19]/46,XY,inv(9)(p12q13)c[1]. Retrospective FISH analysis revealed a cryptic monosomy 7 clone in the initial AML sample. The clone with multiple trisomies was eliminated after induction therapy and never recurred, but a clone with monosomy 7 was still detected in myelodysplastic marrow with a normal blast percentage. Both clones were successfully eliminated after related peripheral blood stem cell transplantation, but the patient died of relapsed AML with monosomy 7. We concluded that one clone was de novo AMoL with chromosome 6, 8, 11, 13, and 19 trisomy and that the other was acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) with chromosome 7 monosomy showing different responses to chemotherapy. Simultaneous onset of cytogenetically unrelated hematological malignancies that each have a different disease status is a rare phenomenon but is important to diagnose for a correct understanding of the disease status and for establishing an appropriate treatment strategy.

[Figure][1] A 31-year-old white man presented with a 6-week history of symptoms of anemia, progressive hearing loss, and periorbital edema. Clinical examination revealed striking periorbital swelling (panels A-B) and periauricular edema with resultant tympanic membrane obstruction. No

Introduction: Isolated leukemic infiltration of peripheral nerves without central nervous system involvement, or isolated neuroleukemiosis, is an extremely rare complication of leukemia. Methods: We report the case of a patient with isolated neuroleukemiosis and review the pertinent literature. Results: A man with a 12-year history of acute monoblastic leukemia presented with median mononeuropathy. Magnetic resonance imaging revealed a thickened median nerve. Nerve biopsy confirmed the diagnosis of leukemic infiltration. Clinical resolution was achieved through local radiation. Only 10 cases of isolated neuroleukemiosis have been reported. Most were in remission from leukemia. Our patient is the only one who was considered clinically cured of leukemia. Conclusions: The presumed pathophysiology of isolated neuroleukemiosis is hematogenous spread of leukemic cells into the peripheral nervous system across the blood–nerve barrier. It should be considered in the differential diagnosis in patients with leukemia who present with neuropathy, even when they are considered to be clinically cured of leukemia. Muscle Nerve 51: 290–293, 2015

Concurrent acute myeloid leukemia (AML) and multiple myeloma (MM) is rare, more so in chemotherapy-naive patients. Concurrent occurrence of these two malignancies portends poor prognosis. Although anthracycline-based AML regimen, allogeneic hematopoietic stem cell transplantation, tipifarnib and bortezomib have shown promising results in small number of patients, there is a lack of established therapy. We describe a case of concurrent AML and MM in a 66-year-old woman and review previously published literature.

Acute myeloid leukemia (AML) is a malignant hematopoietic stem cell disorder which is sub-classified based on bone marrow morphology and the presence of specific genetic abnormalities. One such cytogenetic abnormality is the pericentric inversion (inv) of chromosome 16 which is typically seen in AML M4 with eosinophilia and is associated with a favorable prognosis. We report the inv (16) in a young woman with AML M5 and abnormal eosinophils. This is a rare entity with only about 20 cases being reported till date.

Classical and up-to-date models of hematopoietic lineage determination are briefly reviewed with the focus on myeloid-based models challenging the existence of the common progenitor for T cells, B cells and NK cells. The analysis of immunophenotype of leukemic blast cells seems to be a promising approach for interpreting some controversies in the schemes of normal hematopoiesis. The lite­rature data as well as our own findings in the patients with various types of acute leukemias are in favor of the concept postulating that common myeloid-lymphoid progenitors giving rise to T and B cell branches retain the myeloid potential. The si­milarity of some immunophenotypic features of blast cells in pro-B acute lymphoblastic leukemia and acute monoblastic leukemia is consistent with monocyte origin postulated in the studies of normal hematopoiesis. Study of acute leukemias may be the challenging area of research allowing for new insight into the origin of hematopoietic cell lineages. Key Words: models of hematopoiesis, leukemic stem cell, immunophenotype, acute leukemias.

Background/Aims: It has been demonstrated that KRAS mutations represent about 90% of cancer-associated mutations, and that KRAS mutations play an essential role in neoplastic transformation. Cancer-associated RAS mutations occur frequently in acute myeloid leukemia (AML), suggesting a functional role for Ras in leukemogenesis. Methods: We successfully established a mouse model of human leukemia by transplanting bone marrow cells co-transfected with the K-ras (G12D) mutation and AML1/ETO fusion protein. Results: Mice transplanted with AML/ETO+KRAS co-transduced cells had the highest mortality rate than mice transplanted with AML/ETO- or KRAS-transduced cells (115d vs. 150d). Upon reaching a terminal disease stage, EGFP-positive cells dominated their spleen, lymph nodes, peripheral blood and central nervous system tissue. Immunophenotyping, cytologic analyses revealed that AML/ETO+KRAS leukemias predominantly contained immature myeloid precursors (EGFP+/c-Kit+/Mac-1-/Gr-1-). Histologic analyses revealed that massive leukemic infiltrations were closely packed in dense sheets that effaced the normal architecture of spleen and thymus in mice transplanted with AML1/ETO + KRAS co-transduced cells. K-ras mRNA and protein expression were upregulated in bone marrow cells of the K-ras group and AML1/ETO + Kras group. The phosphorylation of MEK/ERK was significantly enhanced in the AML1/ETO + Kras group. The similar results of the AML1/ETO + Nras group were consistent with those reported previously. Conclusion: Co-transduction of KrasG12D and AML1/ETO induces acute monoblastic leukemia. Since expression of mutant K-ras alone was insufficient to induce leukemia, this model may be useful for investigating the multi-step leukemogenesis model of human leukemia.

A previously healthy eleven month old male Malay infant presented with fever, upper respiratory tract infection and right knee swelling. Pallor, bilateral proptosis, hepatosplenomegaly, multiple scalp swellings and a right cheek swelling were observed. Investigations revealed that he had acute monoblastic leukemia or FAB M5a. Immunophenotyping by flow cytometry showed that the blast cells were positive for CD45, CD13, CD33, HLA-DR, CDllc, CD71, EMA, and Cytokeratin. They were negative for CD34, CD19, CD10, CD22, CD2, CD3, CD4, CD7, CD8, CD61, NK, Glycophorin A, and CD14. The monoblasts were used to evaluate anti-EMA and anti-cytokeratin. They were unexpectedly found to be positive. Acute monoblastic leukaemias are well known to show extramedullary infiltration and this may be their primary mode of presentation. Thus, in immunochemostry, when using EMA and cytokeratin expression in the differential diagnosis of neoplastic diseases, it is important to consider that monoblasts may express these markers as illustrated by this case.