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Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia accompanied by an aggressive clinical course and dismal prognosis. We herein report a case of AMKL preceded by mediastinal germ cell tumor that relapsed early after allogeneic hematopoietic stem cell transplantation with myeloablative conditioning but was successfully treated using salvage cord blood transplantation (CBT) with reduced-intensity conditioning. Although several serious complications developed, sustained remission with a favorable general condition was ultimately achieved. Although an optimal therapeutic strategy remains to be established, the graft-versus-leukemia effect of CBT may be promising, even for the treatment of refractory AMKL.

Identification of fusion genes in clinical routine is mostly based on cytogenetics and targeted molecular genetics, such as metaphase karyotyping, fluorescence in situ hybridization and reverse-transcriptase polymerase chain reaction. However, sequencing technologies are becoming more important in clinical routine as processing time and costs per sample decrease. To evaluate the performance of fusion gene detection by RNAsequencing compared to standard diagnostic techniques, we analyzed 806 RNA-sequencing samples from patients with acute myeloid leukemia using two state-of-the-art software tools, namely Arriba and FusionCatcher. RNA-sequencing detected 90% of fusion events that were reported by routine with high evidence, while samples in which RNA-sequencing failed to detect fusion genes had overall lower and inhomogeneous sequence coverage. Based on properties of known and unknown fusion events, we developed a workflow with integrated filtering strategies for the identification of robust fusion gene candidates by RNA-sequencing. Thereby, we detected known recurrent fusion events in 26 cases that were not reported by routine and found discrepancies in evidence for known fusion events between routine and RNA-sequencing in three cases. Moreover, we identified 157 fusion genes as novel robust candidates and comparison to entries from ChimerDB or Mitelman Database showed novel recurrence of fusion genes in 14 cases. Finally, we detected the novel recurrent fusion gene NRIP1- MIR99AHG resulting from inv(21)(q11.2;q21.1) in nine patients (1.1%) and LTN1-MX1 resulting from inv(21)(q21.3;q22.3) in two patients (0.25%). We demonstrated that NRIP1-MIR99AHG results in overexpression of the 3' region of MIR99AHG and the disruption of the tricistronic miRNA cluster miR-99a/let-7c/miR-125b-2. Interestingly, upregulation of MIR99AHG and deregulation of the miRNA cluster, residing in the MIR99AHG locus, are known mechanisms of leukemogenesis in acute megakaryoblastic leukemia. Our findings demonstrate that RNA-sequencing has a strong potential to improve the systematic detection of fusion genes in clinical applications and provides a valuable tool for fusion discovery.

Down syndrome (DS) is a congenital chromosomal abnormality caused by the presence of all or part of a third copy of chromosome 21 (+21). DS is frequently complicated by congenital heart or digestive tract diseases at birth. DS patients are prone to infections and have mental retardation, with dementia such as Alzheimer's disease showing in later life. Furthermore, malignancies with specific characteristics are also highly reported in DS patients compared with non-DS patients. Therefore, DS is believed to be a cancer predisposition syndrome due to the chromosomal instability. Acute myeloid leukemia (AML) and especially acute megakaryoblastic leukemia (AMKL) by French-American-British (FAB) classification are the most frequent hematological malignancies in DS patients, occurring at a rate that is 500 times higher than that in non-DS patients. Interestingly, transient abnormal myelopoiesis (TAM) is observed in approximately 10% of DS neonates with GATA1 mutations, and most TAM patients are asymptomatic and show spontaneous regression; however, about 10%–20% of TAM cases are fatal because of complications such as fetal effusion, liver fibrosis, and other complications. Acute lymphoblastic leukemia (ALL) is also associated with DS, occurring at a rate that is 20 times higher than that in non-DS patients. Furthermore, the prognosis of DS-ALL patients is poorer than that of non-DS-ALL patients. A recent genetic analysis revealed that more than half of DS-ALL cases have a mutation in the CRLF2–JAK pathway, indicating that JAK inhibitors might have a limited effect for DS-ALL patients. Notably, solid tumors such as neuroblastoma, Wilms tumor, and brain tumor, which are frequently observed in non-DS children, are rarely reported in DS children. The reason remains unknown, but it may be because of the triplication of the Down syndrome critical region 1 (DSCR1) gene on chromosome 21. In adult patients with DS, the expected age-adjusted incidence rates of solid tumors are low compared with age-matched euploid cohorts for most cancers except for testicular cancer. Although the average life expectancy of patients with DS will increase with advances in healthcare, the detailed health problems including cancer rates in older DS patients remain unknown. Therefore, these issues will be needed to be addressed in future studies.

Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML), which is associated with poor prognosis for all patients except children with t(1;22) or Down syndrome. The frequency of complete remission in case of AMKL is comparable to the frequency of complete remission in other variants of AML, and the median survival is much lower. This determines the necessity to update criteria for assessment of the effect of treatment using flow cytometry definition of the level of minimal residual disease (MRD). Nowadays, there are no unified and standardized approaches for the measurement of MRD in case of myeloid leukemia, including AMKL, which prohibits adequate assessment of the therapy effect and in some cases determination of the indications for allogeneic hematopoietic stem cells transplantation. The article identifies diagnostic features and describes approaches for the measurement of the level of MRD in case of AMKL. Aim. The aim is to demonstrate the algorithms for diagnosing and measuring MRD in case of AML-M7 in children. Materials and methods. The article analyzes the clinical and immunological profile of 10 boys and 4 girls with the initial diagnosis of AMKL between the ages of 3 months 12 years old, 13 of them have received treatment in the FSBI N.N. Blokhin National Medical Research Center of Oncology and one in the GBUZ Morozovsky DGKB between 1995 and 2020, The measurement of MRD was carried out in 6 patients. The measurement of MRD was carried out using both morphocytochemical method and multiparameter flow cytometry with megakaryocyte markers (CD61, CD42, CD41) in combination with other myeloid markers (CD13, CD33), CD34, CD117 and aberrant markers (mainly CD7). Results. We showed that adequate measurement of the level of MRD had required detailed immunophenotyping during diagnosis to determine the aberration of megakaryoblasts. CD9 marker (100%), CD33 myeloid marker (69.2%), stem cell antigen CD34 (46.2%), CD13 (38.2%) in addition to megakaryocyte markers (100%) were most often expressed on blast cells in case of AMKL. The CD117 antigen was present on the blasts in 33.3% of cases. The expression of the T-cell-associated CD7 antigen (46.2%) was frequent. The measurement of MRD was carried out during the treatment (usually after an induction course) on the basis of the markers of megakaryocytic cell line (CD61, CD41, CD42a, CD42b), weak CD45 expression, as well as the immunophenotype characteristics during initial diagnosis. The level of MRD ranged from completely negative (0%; 0.006%) to evident (1.05%). Conclusion. The detection of residual tumor megakaryoblasts in case of AML-M7 using flow cytometry is a promising method to evaluate the effect of therapy. The adequate measurement of the level of MRD requires detailed immunophenotyping during the diagnosis to determine the aberration of megakaryoblasts.

Background Acute megakaryoblastic leukemia (AMKL) is a biologically heterogeneous subtype of acute myeloid leukemia that originates from megakaryocytes. Patients with AMKL with non-Down syndrome (DS) had a poorer prognosis. However, clear prognostic indicators and treatment recommendations for this subgroup remain controversial. Patients and Methods Herein, we performed a retrospective study on 40 patients (age ≤ 18 years) with non-Down syndrome AMKL at our institution. We assessed the effect of different prognostic factors, such as their cytogenetic abnormalities, early treatment response, and the role of hematopoietic stem cell transplantation (HSCT) as post-remission treatment on the outcomes. Results The complete remission (CR) rate of the patients was 57.9% and 81.1%, respectively, at the end of induction therapy 1 and 2. The overall survival (OS) and event-free survival rates at 2 years were 41% ± 13% and 41% ± 10%, respectively. An analysis of the cytogenetic features showed that patients with +21 or hyperdiploid (> 50 chromosomes) had significantly better OS than those in other cytogenetic subgroups (Plog-rank = .048 and Plog-rank = .040, respectively). Besides cytogenetics, an excellent early treatment response (CR and minimal residual disease Conclusion AMKL in patients with non-Down syndrome has a poor outcome. With poor OS but CR rates comparable with other acute myeloid leukemia subtypes, allogenic HSCT may be a better option for post-remission therapy than conventional chemotherapy, especially for those having a poor response to induction therapy.

Down syndrome (DS) is the most common chromosomopathy in humans, usually caused by constitutional trisomy 21. It associates with several developmental anomalies, as well as with an increased risk o...

Transient abnormal myelopoiesis (TAM) is a unique hematological syndrome specific for neonates with Down syndrome. Clinical and hematological manifestations of ТАМ are similar manifestations of acute leukemia, but they may resolve spontaneously by few weeks/months after birth. Summation trisomy 21 and GATA1 mutation in blast clone is a required element for development TAM. Presentation of this syndrome occurs in the first days of life; clinical manifestations may be absent (“silent” TAM) or even lead to death of fetus and neonate. The main interest in the study of this issue is the fact that after spontaneous regression there in 20% of cases at the age of 3–4 years developing acute megakaryoblastic leukaemia (AMKL). The basic transformation factors TAM to AMKL are unknown. In this article we represent 6 cases of TAM identified in Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology, and Immunology from 2012 to 2019. Parents of these patients gave their agreement to use personal data in research and publications.

An autopsy case (85-year-old Japanese male) of myeloperoxidase- (MPO-) positive acute myeloid leukemia with maturation (M1) accompanying megakaryocytic differentiation is presented. The patient manifested acute coronary syndrome. Even after emergent percutaneous coronary intervention, his performance status remained poor, so no chemotherapy against leukemia was given. The final white blood cell count reached 291,700/μL, and the platelet count was elevated to 510,000/μL. No cytogenetic studies were performed. He died at the 25th day of hospitalization. Autopsy revealed marked leukemic infiltration to the endocardium and subendocardial myocardium. Subendocardial myonecrosis was surrounded or replaced by the leukemic blasts, and neither granulation tissue reaction nor fibrosis was observed. In the cardiovascular lumen, lard-like blood clots were formed and microscopically consisted of leukemic blasts and platelets (leukemic thrombi). Infiltration of leukemic blasts was seen in the body cavities and systemic organs including the lung. The MPO-positive blasts lacked azurophilic granules and expressed the stem cell markers, CD34 and CD117 (c-kit). No features of myelofibrosis were seen in the 100% cellular marrow. In the endocardium, liver, lymph nodes, and bone marrow, megakaryocytic cells (CD42b/CD61+, MPO-) were distributed, while the small-sized blastic cells in the blood and tissues predominantly expressed MPO. The blasts lacked expression of CD42b/CD61. Megakaryocytic differentiation might be stimulated by certain tissue factors. AML accompanying megakaryocytic differentiation in certain tissues and organs should be distinguished from acute megakaryoblastic leukemia. The mechanisms provoking acute coronary syndrome in acute myeloid leukemia are discussed.

Young males have a unique but rare predilection to develop mediastinal nonseminomatous germ cell tumors (NSGCTs) and concomitant acute megakaryoblastic leukemia (AMKL). Common cytogenetic and molecular abnormalities such as isochromosome 12p and somatic Tumor Protein P53(TP53) and Phosphatase And Tensin Homolog (PTEN) mutations have been reported in the presumed mutual neoplastic clones of origin. We report the case of a 17-year-old male who presented with a mediastinal NSGCT with high-grade sarcomatous transformation and a diagnosis of AMKL approximately 4 months later. Next-generation sequencing revealed identical KRAS Proto-Oncogene, GTPase (KRAS) p.Ala146Thr, TP53 p.Leu257Pro, and PTEN p.Leu181Pro missense mutations at similar variant allele frequencies in both the NSGCT and AMKL samples. Cytogenetic and microarray analyses detected shared copy gains in all chromosomes except chromosomes 9, 13, and Y. Multiple additional clonal chromosomal alterations were detected in the AMKL sample when compared with the NSGCT. This case emphasizes the shared clonal origins of these malignancies and identifies KRAS and other copy number alterations as potential molecular drivers in a subset of these combined diseases.

Long noncoding ribonucleic acids (lncRNAs) are ribonucleic acid (RNA) molecules longer than 200 nucleotides without protein-coding capacity. Several studies have shown that lncRNAs play a pivotal role in the initiation, maintenance, and progression of acute myeloid leukemia (AML), which could make them a promising candidate in the diagnosis and treatment of leukemia. Acute Megakaryoblastic leukemia (AMKL) is a rare form of AML with a poor prognosis and low survival. It has been reported that lncRNA MIR100HG is involved several types of malignancies. In the present study, MIR100HG was downregulated in a human acute megakaryoblastic leukemia cell line (M-07e) using Antisense LNA GapmeRs. In order to assess the expression level of MIR100HG, cell viability, apoptosis, and necrosis (late apoptosis), quantitative reverse transcription polymerase chain reaction (qRT-PCR), Methyl-thiazol Tetrazolium assay, AnnexinV, and propidium iodide staining was performed at different time points after the transfection. In addition, the expression level of TGFβ was evaluated by qRT-PCR. Our results revealed that inhibition of MIR100HG might serve as a new method for inhibition of the proliferation of AMKL cells and therefore, could be a promising approach in medicine for targeted therapy in AMKL.

Reactive myelofibrosis (MF) may be associated with infectious, inflammatory, or neoplastic conditions. Extensive myelofibrosis and indolent course are frequent in acute megakaryoblastic leukemia, but these findings are rarely reported in acute promyelocytic leukemia (APL). Patients with neoplastic disorders associated with MF are reported to have an inferior outcome. However, the effect of this association is not apparent in APL patients. This report presents a case of APL in a pediatric patient in association with significant reticulin fibrosis and osteosclerosis. The case highlights that fibrosis in the marrow can make it more challenging to diagnose acute leukemia. The PML-RARA transcripts can be present with subtle clinical or hematological findings, emphasizing the importance of molecular studies in unexplained cytopenias. Furthermore, in the case of APL, as opposed to other myeloid neoplasms, fibrosis does not appear to be associated with a worse prognosis and can resolve after treatment.

Acute megakaryoblastic leukemia (AMKL) represents ∼10% of pediatric acute myeloid leukemia cases and typically affects young children (

Myeloid leukemia associated with Down syndrome (ML-DS) is characterized by a predominance of acute megakaryoblastic leukemia, the presence of GATA1 mutations and a favorable outcome. Because DS children can also develop conventional acute myeloid leukemia with unfavorable outcome, detection of GATA1 mutations is important for diagnosis of ML-DS. However, myelofibrosis and the significant frequency of dry taps have hampered practical screening of GATA1 mutations using bone marrow (BM) samples. In response to those problems, 82 patients were enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-D11 study. GATA1 mutations were analyzed by Sanger sequencing (SS) using genomic DNA (gDNA) from BM and cDNA from peripheral blood (PB) followed by targeted next-generation sequencing (NGS) using pooled diagnostic samples. BM and PB samples were obtained from 71 (87%) and 82 (100%) patients, respectively. GATA1 mutations were detected in 46 (56%) and 58 (71%) patients by SS using BM gDNA and PB cDNA, respectively. Collectively, GATA1 mutations were identified in 73/82 (89%) patients by SS. Targeted NGS detected GATA1 mutations in 74/82 (90%) patients. Finally, combining the results of SS with those of targeted NGS, GATA1 mutations were identified in 80/82 (98%) patients. These results indicate that SS using BM gDNA and PB cDNA is a rapid and useful method for screening for GATA1 mutations in ML-DS patients. Thus, a combination of SS and targeted NGS is a sensitive and useful method to evaluate the actual incidence and clinical significance of GATA1 mutations in ML-DS patients.

Acute megakaryocytic leukemia (AMKL) is a rare type of acute myeloid leukemia (AML), which is characterized by its effect on megakaryocytes in bone marrow. Despite standard doses of anthracycline plus cytarabine based regimen, AMKL is notorious for its poor prognosis. With the continuous development of targeted drugs, the choice of chemotherapy regimens for AML patients has been gradually enriched. However, as far as we known, there is little data with this regimen in AMKL with decitabine and Bcl-2 inhibitor combined with imatinib. Herein, we reported the first case of adult AMKL with BCR-ABL positive successfully treated with decitabine and venetoclax combined with imatinib.

BackgroundA high ecotropic viral integration site 1 (EVI1) expression (EVI1high) is an independent prognostic factor in adult acute myeloid leukemia (AML). However, little is known of the prognostic value of EVI1high in pediatric AML. This study aimed to examine the biological and prognostic significance of EVI1high in uniformly treated pediatric patients with AML from a large cohort of seven centers in China.MethodsA diagnostic assay was developed to determine the relative EVI1 expression using a single real-time quantitative polymerase chain reaction in 421 newly diagnosed pediatric AML patients younger than 14 years from seven centers in southern China. All patients were treated with a uniform protocol, but only 383 patients were evaluated for their treatment response. The survival data were included in the subsequent analysis (n = 35 for EVI1high, n = 348 for EVI1low).ResultsEVI1high was found in 9.0% of all 421 pediatric patients with de novo AML. EVI1high was predominantly found in acute megakaryoblastic leukemia (FAB M7), MLL rearrangements, and unfavorable cytogenetic aberrance, whereas it was mutually exclusive with t (8; 21), inv (16)/t (16; 16), CEBPA, NPM1, or C-KIT mutations. In the univariate Cox regression analysis, EVI1high had a significantly adverse 5-year event-free survival (EFS) and overall survival (OS) [hazard ratio (HR) = 1.821 and 2.401, p = 0.036 and 0.005, respectively]. In the multivariate Cox regression analysis, EVI1high was an independent prognostic factor for the OS (HR = 2.447, p = 0.015) but not EFS (HR = 1.556, p = 0.174). Furthermore, EVI1high was an independent adverse predictor of the OS and EFS of patients with MLL rearrangements (univariate analysis: HR = 9.921 and 7.253, both p < 0.001; multivariate analysis: HR = 7.186 and 7.315, p = 0.005 and 0.001, respectively). Hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) provided EVI1high patients with a tendential survival benefit when compared with chemotherapy as a consolidation (5-year EFS: 68.4% vs. 50.8%, p = 0.26; 5-year OS: 65.9% vs. 54.8%, p = 0.45).ConclusionIt could be concluded that EVI1high can be detected in approximately 10% of pediatric AML cases. It is predominantly present in unfavorable cytogenetic subtypes and predicts adverse outcomes. Whether pediatric patients with EVI1high AML can benefit from HSCT in CR1 needs to be researched further.

Acute megakaryocytic leukemia (AMKL) is a rare type of acute myeloid leukemia (AML), which is characterized by its effect on megakaryocytes in bone marrow. Despite standard doses of anthracycline plus cytarabine based regimen, AMKL is notorious for its poor prognosis. With the continuous development of targeted drugs, the choice of chemotherapy regimens for AML patients has been gradually enriched. However, as far as we known, there is little data with this regimen in AMKL with decitabine and Bcl-2 inhibitor combined with imatinib. Herein, we reported the first case of adult AMKL with BCR-ABL positive successfully treated with decitabine and venetoclax combined with imatinib.

Infant acute leukemia is a rare but aggressive disease. Although infant acute leukemia is cytologically and histologically similar to acute leukemia seen in older children and adults, it displays unique and characteristic clinical and genetic characteristics. The features, as well as the extremely young age of the patients, present multiple challenges for treatment. This review focuses on the unique pathology of acute leukemia of infancy, including the genetic characteristics that are specific for these diseases.

International audience; Pediatric acute myeloid leukemia is a rare and heterogeneous disease in relation to morphology, immunophenotyping, germline and somatic cytogenetic and genetic abnormalities. Over recent decades, outcomes have greatly improved, although survival rates remain around 70% and the relapse rate is high, at around 30%. Cytogenetics is an important factor for diagnosis and indication of prognosis. The main cytogenetic abnormalities are referenced in the current WHO classification of acute myeloid leukemia, where there is an indication for risk-adapted therapy. The aim of this article is to provide an updated review of cytogenetics in pediatric AML, describing well-known WHO entities, as well as new subgroups and germline mutations with therapeutic implications. We describe the main chromosomal abnormalities, their frequency according to age and AML subtypes, and their prognostic relevance within current therapeutic protocols. We focus on de novo AML and on cytogenetic diagnosis, including the practical difficulties encountered, based on the most recent hematological and cytogenetic recommendations.

Coexistent myelodysplastic syndrome and acute megakaryoblastic leukemia is an aggressive disease which often do not respond to standard chemotherapy due to the various molecular and cytogenetic abnormalities. Understanding of the molecular pathogenesis may lead to better therapeutic modalities as current conventional therapies are largely ineffective.

Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia, in which the bone marrow produce increased numbers of immature abnormal megakaryoblasts. AMKL is rare both in children and adults, but is the most frequent subtype of acute myeloid leukemia (AML) in children with Down syndrome. Morphological diagnosis of this disease could be complicated, thus flow cytometry plays a crucial role in the diagnostics of AMKL. The aim of the present study was to investigate the immunophenotypic characteristics of AMKL in children. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The study group included 103 patients with AMKL. Antigen expression profile was assessed by multicolor flow cytometry. We identified three groups of patients according to different levels of CD45 expression, and in majority of patients (74%) high level of CD45 expression was detected. Significant immunophenotypic differences between these groups were found. In 56% of patients trisomy of 21 chromosome was detected. Among these patients, 86% belonged to group of high CD45 expression. Moreover, children with trisomy 21 represented the majority in the group with high level of CD45 expression (64%). Also, there were found several significant differences between patients with and without trisomy 21 within the group of high CD45 expression. This study demonstrated the wide immunophenotypic heterogeneity of AMKL. In general, the revealed diversity obviously reflects the biological heterogeneity of this AML subtype.

GLI-similar 1-3 (GLIS1-3), a subfamily of Krüppel-like zinc finger transcription factors, function as key regulators of several biological processes important to oncogenesis, including control of cell proliferation, differentiation, self-renewal, and epithelial-mesenchymal transition. This review provides a short overview of the critical roles genetic changes in GLIS1-3 play in the development of several malignancies. This includes intrachromosomal translocations involving GLIS2 and ETO2/CBFA2T3 in the development of pediatric non-Down's syndrome (DS), acute megakaryoblastic leukemia (AMKL), a malignancy with poor prognosis, and an association of interchromosomal translocations between GLIS3, GLIS1, and PAX8, and between GLIS3 and CLPTM1L with hyalinizing trabecular tumors (HTTs) and fibrolamellar hepatocellular carcinoma (FHCC), respectively. Targeting upstream signaling pathways that regulate GLIS signaling may offer new therapeutic strategies in the management of cancer.

Acute megakaryoblastic leukemia (AMegL) is a rare hematological neoplasm most often diagnosed in children and is commonly associated with Down's syndrome (DS). Although AMegLs are specifically characterized and typically diagnosed by megakaryoblastic expansion, recent advancements in molecular analysis have highlighted the heterogeneity of this disease, with specific cytogenic and genetic alterations characterizing different disease subtypes. Areas covered: This review will focus on describing recurrent molecular variations in both DS and non-DS pediatric AMegL, their role in promoting leukemogenesis, their association with different clinical aspects and prognosis, and finally, their influence on future treatment strategies with a number of specific drugs beyond conventional chemotherapy already under development. Expert opinion: Deep understanding of the genetic and molecular landscape of AMegL will lead to better and more precise disease classification in terms of diagnosis, prognosis, and possible targeted therapies. Development of new therapeutic approaches based on these molecular characteristics will hopefully improve AMegL patient outcomes.

Acute Megakaryoblastic Leukemia (AMKL) is a subtype of acute myeloid leukemia triggered by megakaryocytes. Acute megakaryoblastic leukemia is divided into three groups, AMKL in children with Down syndrome (DS-AMKL), AMKL in children who do not have Down Syndrome (non-DS-AMKL), and AMKL in non-DS adults (AMKL adults).The basis of the diagnosis of AMKL or AML-M7, according to FAB, is the presence of megakaryocyte line cells as many as 30% or more of all cells. Meanwhile, the diagnosis of AMKL, according to the 2016 WHO guidelines, is acute leukemia with blasts, about > 20%, > 50% of which is megakaryocyte line cells. Megakaryocyte cells can be more clearly seen with electron microscopes that react positively to platelet peroxidase or use marker antibodies to CD41/gpIIb, CD42b/gpIb, CD61/gpIIIa, von Willebrand factors, and linker for T cell activation.Based on the results of this research, there are differences in cytogenetics between the three types of AMKL according to their different pathophysiology. The World Health Organization (WHO) argued that AMKL was categorized into not otherwise specific (NOS) AML criteria. These criteria exclude AML with myelodysplasia (AMLMRC), AML associated with therapy, and AML with recurrent genetic abnormalities, such as AML with t (1; 22) (p13.3; q13.1), inv (3) (q21.3q26.2), or t (3; 3) (q21.3; q26.2). DS-AMKL is also classified into myeloid leukemia associated with DS. In conclusion, AMKL in adults is not only considered as a rare subtype of AMKL, only 1% of AML cases in population-based clinical experiments and data but also has a poor prognosis.

Acute megakaryoblastic leukemia is a rare subtype of pediatric acute myeloid leukemia (AML) with poor outcomes in patients with non-Down syndrome. The reported outcomes have been poor, and the prognostic factors have not been clearly determined.To evaluate the prognostic significance of various cytogenetic abnormalities and minimal residual disease status determined by flow cytometry after induction I, we retrospectively analyzed the data of 80 patients with non-Down syndrome with a diagnosis of M7 AML treated at Children's Cancer Hospital Egypt (CCHE-57357) from July 2007 through December 2016.Of the 80 patients, 15 died during induction I and were excluded from the survival analysis. The overall survival, event-free survival, and cumulative incidence of relapse at 2 years was 52.6% ± 12.7%, 45.2% ± 12.3%, and 31.8% ± 11.5% respectively. Of the 90 patients, 61 had cytogenetic abnormalities, including trisomy 19,13q, trisomy 8, complex karyotype, t(1;22), KMT2A rearrangements, and trisomy 21. None of these had an effect on the outcomes. In addition, 34 patients had minimal residual disease 0.1% after induction I, but the difference did not reach statistical significance. Patients with a delayed time to recovery (possibly due to myelofibrosis) had worse outcomes compared with those with early recovery (47% ± 19.2% vs. 63.2% ± 21.9%, respectively).Acute megakaryoblastic leukemia in patients with non-Down syndrome has a poor outcome with no clearly defined prognostic factors. However, future directions to risk stratify and tailor therapy should include assessment of the tumor biology according to the molecular pathways and study of the pathogenesis of myelofibrosis in this disease, which could affect the prognosis.

We report the case of a 3-year-old girl diagnosed with acute megakaryoblastic leukemia, who presented after >1 year of bilateral leg pain. At times the pain was severe enough to prevent ambulation, prompting visits to her primary care provider. However, it was not until acute respiratory failure occurred with subsequent hospitalization in the pediatric intensive care unit that severe anemia and thrombocytopenia were discovered and the diagnosis of acute myeloid leukemia was made. Bilateral lower extremity swelling was noted on admission and radiographs showed diffusely abnormal appearance of the long bones of her lower extremities with periosteal reaction and echogenic debris in the subperiosteal space, thought to represent leukemic cells. This case highlights the importance of recognizing atypical signs and symptoms of myelodysplastic syndrome progressing to acute leukemia in the context of abnormal bone pain and radiographic changes.

Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia but is approximately 500 times more likely to develop in children with Down syndrome (DS) through transformation of transient abnormal myelopoiesis (TAM). This study investigates the clinical significance of genomic heterogeneity of AMKL in children with and without DS and in children with TAM. Genomic evaluation of nine patients with DS-related TAM or AMKL, and six patients with non-DS AMKL, included conventional cytogenetics and a comprehensive next-generation sequencing panel for single-nucleotide variants/indels and copy-number variants in 118 genes and fusions involving 110 genes. Recurrent gene fusions were found in all patients with non-DS, including two individuals with complex genomes and either a NUP98–KDM5A or a KMT2A–MLLT6 fusion, and the remaining harbored a CBFA2T3–GLIS2 fusion, which arose from both typical and atypical cytogenetic mechanisms. These fusions guided treatment protocols and resulted in a change in diagnosis in two patients. The nine patients with DS had constitutional trisomy 21 and somatic GATA1 mutations, and those with DS-AMKL had two to four additional clinically significant somatic mutations. Comprehensive genomic characterization provides critical information for diagnosis, risk stratification, and treatment decisions for patients with AMKL. Continued genetic and clinical characterization of these rare cancers will aid in improving patient management.

A 59-year old gentleman with transformation of myelodysplastic syndrome to acute megakaryoblastic leukemia was treated with standard intensive chemotherapy. His poor outcome was attributed to advanced age, aggressive disease biology, underlying myelodysplastic syndrome, poor response to induction chemotherapy, high lactate dehydrogenase and lack of good cytogenetic and molecular mutations.

The work is devoted to the classification of tumor lesions of the hematopoietic organs - bone marrow and lymphoid system. These lesions are called hemopoietic neoplasia (hemoblastosis). Hemopoietic neoplasia is divided into leukecmia (leucosis) and lymphoma (hematosarcoma). Leukemia is a systemic blood disease of a tumor nature with primary bone marrow damage. Lymphomas are tumors of lymphoid cells with primary extra-bone marrow localization and localized tumor growth. Leukemias are divided into myeloid and lymphoid. Myeloids arise as a result of clonal proliferation of malignant progenitor cells of the myeloid series - CFU-GEMM, or its descendants. Lymphoid - as a result of proliferation of malignant progenitor cells of lymphoid series - CFU-L, or its descendants. Myeloid disorders include strictly myeloid (granulocytic), erythrocytic, monocytic, megakaryocytic leukemias, and myelodysplastic syndromes. Lymphoid leukemias are divided into T-cell, B-cell and plasma-cell. Leukemias are also divided into acute and chronic. Acute is called leukemia, in which the substrate of tumor growth form immature, blastic cells of I-IV classes of hematopoiesis, that lose their ability to maturation (differentiation). In chronic leukemia, this substrate consists of maturing and mature cells of V-VI classes of hematopoiesis, which have retained the ability to mature. The article presents a schematic classification of leukemias developed by the authors, which is based on modern conceptions about the pedigree of tumor cell clones. In 3 tables the FAB-classification of leukemias, adapted in 1991 by American Society of Veterinary Clinical Pathology (ASVCP) to the needs of veterinary medicine is stated. It is shown that today, along with morphological features, cytochemical (enzymatic) and immunological (genetic) markers are increasingly used for more detailed classification. The classification of hemopoietic neoplasias of certain species of domestic animals – cattle, sheeps, cats, dogs, horses, birds, etc. is also considered. Brief data on the prevalence of these diseases in them are given. References are given to the latest improvements and further development of the classifications of leukemias and lymphomas, in particular the revision of these WHO classifications in 2016.

Transient abnormal myelopoiesis (TAM) is a unique clonal myeloproliferation characterized by immature megakaryoblasts that occurs in 5–10% of neonates with Down syndrome (DS). Although TAM regresses spontaneously in most patients, approximately 20% of TAM cases result in early death, and approximately 20% of survivors develop acute megakaryoblastic leukemia (AMKL). We retrospectively reviewed records of 35 DS patients with TAM to determine the correlation between clinical characteristics and blast percentage. Thirteen of the 35 patients were classified as low blast percentage TAM (LBP-TAM), defined as TAM with a peak peripheral blast percentage ≤ 10%. Although no patient with LBP-TAM experienced systemic edema, disseminated intravascular coagulation, or early death, eight patients had elevated direct bilirubin levels (> 2 mg/dl) and one developed AMKL. All patients with LBP-TAM had serum markers of liver fibrosis that exceeded the normal limits, and two patients underwent liver biopsy to clarify the etiology of pathological jaundice. Taken together, our results suggest that patients with LBP-TAM may be at risk of liver fibrosis and liver failure, similarly to patients with classical TAM. Although these patients generally have a good prognosis, they should be carefully monitored for potential development of liver disease and leukemia.

Background There is no established effective treatment for patients with t(1;22)(p13;q13) acute megakaryoblastic leukemia (AMKL) and hepatic fibrosis. Observation Here we report the outcomes of 2 t(1;22)(p13;q13) AMKL patients with hepatic fibrosis. One patient died from liver failure despite the control of leukemia. The other patient was successfully treated with reduced-intensity chemotherapy and antifibrosis therapy with tretinoin and α-tocopheryl acetate, the hepatic fibrosis resolved and leukemia was in remission for 3 years. Conclusions Reduced-intensity chemotherapy plus antifibrosis therapy with tretinoin and α-tocopheryl acetate could be a treatment option for these patients with t(1;22)(p13;q13) AMKL and hepatic fibrosis.

Background Forced polyploidization is an effective strategy for acute megakaryoblastic leukemia (AMKL) therapy and factors controlling polyploidization are potential targets for drug development. Although bone morphology protein 2-inducible kinase (BMP2K) has been implied to be a potential target for fasudil, a potent polyploidy-inducing compound, the function of BMP2K in megakaryopoiesis and AMKL remains unknown. This study aimed to investigate the role of BMP2K as a novel regulator in megakaryocyte polyploidization and differentiation and its implication in AMKL therapy. Results BMP2K upregulation was observed in human megakaryopoiesis and leukemia cells whereas BMP2K was downregulated in AMKL cells forced to undergo terminal differentiation. Functionally, BMP2K suppressed MLN8237-induced megakaryocytic differentiation in AMKL cells and dampened megakaryocyte differentiation in primary mouse fetal liver cells. Furthermore, BMP2K overexpression conferred resistance to multiple chemotherapy compounds in AMKL cells. Mechanistically, cyclin-dependent kinase 2 (CDK2) interacted with BMP2K and partially mediated its function. In transient MLN8237 and nocodazole challenge cell model, BMP2K reduced cell percentage of G2/M phase but increased G1 phase, suggesting a role of BMP2K antagonizing polyploidization and promoting mitosis by regulating cell cycle in megakaryopoiesis. Conclusions BMP2K negatively regulates polyploidization and megakaryocyte differentiation by interacting CDK2 and promoting mitosis in megakaryopoiesis. BMP2K may serve as a potential target for improvement of AMKL therapy.

MicroRNAs (miRNAs) are non-coding RNAs involved in post-transcriptional regulation of gene expression. In many cancers, up- or downregulation of different miRNAs is reported. In acute myeloid leukemia, upregulation of miR-92a-3p was reported in human in vitro studies. We performed blockage of miR-29a-3p in human acute megakaryoblastic leukemia cell line (M-07e) by using locked nucleic acid (LNA) and cell proliferation; apoptosis and necrosis were assessed. At different time points after LNA-anti-miR92a-3p transfection, miR-92a-3p quantitation was assessed by qRT-real-time PCR, MTT assay and annexin/propidium iodide staining were performed. The data were processed using the ANOVA test. At all three time points, the expression of miR-92a-3p was lower in the LNA-anti-miR group compared with the control groups. Cell viability between LNA-Anti-miR and the control group was statistically significant. Blockage of miR-92a-3p was associated with increment of the ratio of apoptotic cells in the LNA-anti-miR group was higher than the other group. The ratio of necrotic cells in the LNA-antimiR group was higher than the other groups. These assessments indicate that miR-92a-3p blockage can decrease the viability of M-07e cells, which is mainly due to induction of apoptosis and necrosis. Our findings could open up a path to a miRNA based therapeutic approach for treatment of acute megakaryoblastic leukemia.

Background The occurrence of a mediastinal germ cell tumor (GCT) and hematological malignancy in the same patient is very rare. Due to its rarity, there have been only two reports of the concurrent cases undergoing detailed genetic analysis with whole-exome sequencing (WES), and the possible clonal relationship between the both tumors remained not fully elucidated. Methods We performed whole-exome sequencing analysis of mediastinal GCT and acute myeloid leukemia (AML) samples obtained from one young Japanese male adult patient with concurrent both tumors, and investigated the possible clonal relationship between them. Results Sixteen somatic mutations were detected in the mediastinal GCT sample and 18 somatic mutations in the AML sample. Mutations in nine genes, including TP53 and PTEN both known as tumor suppressor genes, were shared in both tumors. Conclusions All in our case and in the previous two cases with concurrent mediastinal GCT and AML undergoing with whole-exome sequencing analysis, TP53 and PTEN mutations were commonly shared in both tumors. These data not only suggest that these tumors share a common founding clone, but also indicate that associated mediastinal GCT and AML harboring TP53 and PTEN mutations represent a unique biological entity.

Objectives Immunohistochemistry (IHC) staining of core biopsy sections often plays an essential role in the diagnosis of acute megakaryoblastic leukemia (AMKL). The goal of this study was to define the relative sensitivities of commonly used stains for markers of megakaryocytic differentiation. Methods The sensitivities of IHC stains for CD42b, CD61, and von Willebrand factor (vWF) were compared in 32 cases of pediatric AMKL. Results The sensitivities of CD42b, CD61, and vWF were 90.6%, 78.1% and 62.5%, respectively. When CD42b and CD61 were used together, the combined sensitivity increased to 93.6%. There were no cases in which vWF was positive when both CD42b and CD61 were negative. Conclusions CD42b can reliably be used as a solitary first-line marker for blasts of megakaryocytic lineage, whereas CD61 may be reserved for infrequent cases that are CD42b negative. There is no role for the routine use of vWF when CD42b and CD61 are available.

This case report presents a 14-month-old female Poodle mix with acute megakaryoblastic leukemia based on a marked thrombocytosis, abnormal platelet morphology, circulating dwarf megakaryocytes, and blast cells in the blood. Bone marrow abnormalities included dysmegakaryopoiesis dygranulopoiesis, and an increased number of blast cells was observed in the blood. Extensive leukemic involvement was also found in the liver, spleen, lymph nodes, lungs, kidneys, and brain. The cytopathologic features of the abnormal circulating cells were highly suggestive of being megakaryocytic in origin, which was supported by negative myeloperoxidase staining and positive von Willebrand factor staining on immunocytochemistry (ICC). The neoplastic cells were also CD61 positive and had variable von Willebrand factor expression on ICC. Although there were only 25% blast cells in the bone marrow, which theoretically supported myelodysplastic syndrome, the hypothesis that this case represented acute myeloid leukemia of megakaryoblastic origin was confirmed by the continuous increase in circulating blast cell numbers during follow-up visits and the extensive leukemic involvement of parenchymal organs.

An 87-year-old woman not known to have either a lymphoma or leukemia developed a left multinodular, fish-flesh superior epibulbar and forniceal mass. A biopsy disclosed a blastic tumor with scattered multinucleated immature megakaryoblasts. Immunophenotyping of bone marrow cells revealed strong positivity for CD7, CD31, CD43, CD45, CD61, and CD117; CD71, myeloperoxidase, and lysozyme were also positive in scattered cells. Forty percent of the neoplastic cells were Ki-67 positive. Cytogenetic studies indicated a trisomy 8 (associated with worse prognosis) and a t(12; 17) translocation. Desmin, smooth muscle actin, pancytokeratin, CAM 5.2, adipophilin, tryptase, S100, SOX10, MART1, and E-cadherin were negative, ruling out a nonhematopoietic tumor. The conjunctival lesion was diagnosed as a myeloid sarcoma with megakaryoblastic differentiation, a rare variant. It probably arose from a myelodysplastic syndrome. This is the first case of its type to develop in the conjunctiva.

The first event in origination of many childhood leukemias is a specific preleukemic fusion gene (PFG) that arises, often in utero, in hematopoietic stem/progenitor cells (HSPC) from misrepaired DNA double strand break (DSB). An immanently elevated level of DSB and impaired apoptosis may contribute to origination and persistence of PFG and donor cell-derived leukemia in recipients of allogeneic transplantation of umbilical cord blood (UCB). We investigated DSB, apoptosis and PFG in the backtracked UCB cells of leukemic patients. RNA from UCB of three patients with acute lymphoblastic leukemia, patient with acute megakaryoblastic leukemia and Down syndrome, and four healthy children was screened for common PFG by RT-qPCR. Presence of PFG was validated by sequencing. Endogenous γH2AX and 53BP1 DNA repair foci, cell populations, and apoptosis were analyzed in UCB CD34+/- cells with imaging and standard flow cytometry. We found MLL2-AF4 and BCR-ABL (p190) fusion genes in UCB of two out from four pediatric patients, apparently not detected at diagnosis, while UCB cells of TEL-AML1+ ALL patient were tested negative for this PFG and no PFG were detected in UCB cells of healthy children. No significant difference in DNA damage and apoptosis between UCB CD34+/- cells from healthy children and leukemic patients was observed, while Down syndrome trisomy increased DNA damage and resulted in distribution of cell populations resembling transient abnormal myelopoiesis. Our findings indicate increased genetic instability in UCB HSPC of leukemic patients and may be potentially used for diagnostics and exclusion of possibly affected UCB from transplantation.

The advent of large scale genomic sequencing technologies significantly improved the molecular classification of acute megakaryoblastic leukaemia (AMKL). AMKL represents a subset (∼10%) of high fatality pediatric acute myeloid leukemia (AML). Recurrent and mutually exclusive chimeric gene fusions associated with pediatric AMKL are found in 60%-70% of cases and include RBM15-MKL1, CBFA2T3-GLIS2, NUP98-KDM5A and MLL rearrangements. In addition, another 4% of AMKL harbor NUP98 rearrangements (NUP98r), with yet undetermined fusion partners. We report a novel NUP98-BPTF fusion in an infant presenting with primary refractory AMKL. In this NUP98r, the C-terminal chromatin recognition modules of BPTF, a core subunit of the NURF (nucleosome remodeling factor) ATP-dependent chromatin-remodeling complex, are fused to the N-terminal moiety of NUP98, creating an in frame NUP98-BPTF fusion, with structural homology to NUP98-KDM5A. The leukemic blasts expressed two NUP98-BPTF splicing variants, containing one or two tandemly spaced PHD chromatin reader domains. Our study also identified an unreported wild type BPTF splicing variant encoding for 2 PHD domains, detected both in normal cord blood CD34+ cells and in leukemic blasts, as with the fly BPTF homolog, Nurf301. Disease course was marked by rapid progression and primary chemoresistance, with ultimately significant tumor burden reduction following treatment with a clofarabine containing regimen. In sum, we report 2 novel NUP98-BPTF fusion isoforms that contribute to refine the NUP98r subgroup of pediatric AMKL. Multicenter clinical trials are critically required to determine the frequency of this fusion in AMKL patients and explore innovative treatment strategies for a disease still plagued with poor outcomes.

Acute Megakaryoblastic Leukemia (FAB AML M7) occurs in all age groups with two peaks in distribution. The one is in adults and theother in children 1 to 3 years of age especially in those with Down's syndrome. The diagnosis of AML M7 requires more than 30% of thenucleated bone marrow cells being megakaryoblasts. The AML M7 was under diagnosed before the availability of monoclonal antibodies.The more common types of AML MO-M6 have to be excluded by morphological and cytochemical analysis whereas immunology is neededto exclude ALL. The megakaryocytic nature of the leukemia has to be proven by ultrastructural demonstration of platelet peroxidase or byimmunological demonstration of CD61, CD42, CD41 on the surface of the leukemic blasts. Megakaryocytic/megakaryoblastic leukemiasshow a wide morphologic spectrum. Cytoplasmic blebs and protrusions are the most prominent feature of many cases. The nuclei ofthese cells are round with more finely reticulated chromatin and with prominent nucleoli. The megakaryoblastic nature of these cells canbe suggested by morphology. Cytochemistry is of limited diagnostic value in megakaryoblastic leukemias. Usually it is used to excludethe more common types of leukemia. An eighteen months girl was admitted to hospital with anemia and hepatosplenomegaly. There isdismorphic - hypertelorism face and enlargement of neck lymph nodes. The laboratory examination found anemia, hyperleukocytosis with75 % blast cells. Morphologically the blast cells show prominent blebs and cytoplasmic budding resemble features of budding platelets.The cytochemistry staining for granulocyte and erythrocyte lineages were negative. The expressions of lymphoid and myeloid lineagesmarkers by immunoflowcytometry method were also negative. Cytogenetic examination was followed. The physical and laboratoryexamination result conclude a child with Acute Megakaryoblastic Leukemia. Cytogenetic examination was followed

A 64-year-old man with acute myeloid leukemia underwent umbilical cord blood transplantation (UCBT). After 11 months of complete remission (CR) following UCBT, the bone marrow showed 7.5% myeloblasts. CR was obtained after a single course of azacitidine monotherapy, but the myeloblasts gradually increased in the blood. We made a diagnosis of acute megakaryoblastic leukemia derived from donor cell with a fluorescence in situ hybridization (FISH) analysis of the sex chromosomes and an immunophenotypic analysis. Azacitidine was administered again and produced a therapeutic effect of stable disease. This case suggests that azacitidine may be a useful therapy for patients with acute megakaryoblastic leukemia in situations in which intensive chemotherapy and transplantation are not indicated.

Background The functions of the HOXA 5, HOXA 9, and PRDM16 are concerned with embryonic growth and the regulation of adult hematopoietic cells differentiation. The HOXA5, HOXA9, and PRDM16 are expressed in the majority of solid cancers and several hematological malignancies, including myeloproliferative disease and acute leukemia. The function and prognostic values of HOXA5, HOXA9, and PRDM16 quantitative PCR expression in novel patients with acute myeloblastic leukemia (AML) were to be studied. Methods This prospective case-control study was performed on 60 newly diagnosed AML patients and 40 healthy subjects acting as a control group. The patients underwent CBC, BM analysis, HOXA5, HOXA9, and PRDM16 expression by qRT-PCR testing. Results High expressions of HOXA5, HOXA9, and PRDM16 were significantly prevalent in patients compared with the control. The highest incidence of expression was found in AML patients with minimal maturation and acute megakaryoblastic leukemia (M1/M7). Interestingly, high levels of HOXA5, HOXA9, and PRDM16 expressions were correlated with older age and hepatosplenomegaly associated with poor clinical outcome, shorter overall and disease-free survival than low levels of HOXA5, HOXA9, and PRDM16 expressions. Conclusion High HOXA and PRDM16 expressions predict bad outcomes and are associated with weak prognostic factors which can promote new therapeutic trends for AML.

CBFA2T3-GLIS2 is an oncogenic fusion gene that acts as the driver mutation in ~18% of pediatric patients with acute megakaryoblastic leukemia (AMKL) that do not have Down syndrome. CBFA2T3-GLIS2 driven leukemia carries the worst prognosis among all pediatric acute myeloid (AML) subtypes, with event free and overall survival probabilities of 8% and 14% respectively. Chemotherapy and stem cell transplantation fail to cure this disease, thus innovative treatment approaches are needed. While monoclonal antibody and chimeric antigen receptor T-cell (CAR-T) therapies have proven successful in acute lymphoblastic leukemia (ALL), similar successes haven't been realized in AML due to the lack of targetable antigens that eradicate leukemia cells while minimizing off target toxicities such as depletion of normal myeloid cells which can lead to prolonged neutropenia. An alternative is T cell receptor engineered T cell (TCR-T) immunotherapy which use heterodimers consisting of alpha and beta peptide chains to recognize polypeptide fragments presented by MHC molecules on the tumor cells. An advantage of this approach is the ability to recognize intracellular tumor specific and tumor associated antigen fragments in addition to extracellular proteins which results in a wider range of targets. To investigate the immunogenicity of CBFA2T3-GLIS2 positive AMKL cells, we established a humanized patient derived xenograft (PDX) murine model by conditioning 15 immunodeficient NSG-SGM3 mice with 200 rads 24 hours prior to transplantation of 3.5 million CBFA2T3-GLIS2 positive PDX cells derived from an individual female patient. After 20 days of engraftment, 2.5 million HLA class I matched PBMCs from an unrelated female donor were introduced. Experimental mice (engrafted with both PDX cells and PBMCs), leukemia only control mice, and PBMC only control mice were sacrificed at days 30, 35, and 40. Flow cytometry analysis at day 40 showed dramatic reduction of leukemic blasts (huCD45lo, huCD34+) when exposed to PBMCs compared to the leukemia only control (1.48% and 93.7%, respectively). Circulating human Granzyme A was elevated at day 40 in the PDX mice with PBMCs compared to the PBMC only control (9665.4 pg/ml vs. 789.7 pg/ml, p Disclosures Gruber: Kura Oncology: Consultancy.

Objective Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML) associated with poor prognosis for all patients except children with t(1;22) or Down syndrome. The frequency of complete remission in case of AMKL is comparable to the frequency of it in other variants of AML but the median survival is much lower. This determines the necessity of more thorough evaluation of treatment effect using flow cytometry accessment of minimal residual disease (MRD). Methodology The clinical and immunological profile of 8 girls and 9 boys with de novo AMKL between the ages of 3 months–11 years old was analyzed. The primary leucocytosis median was 10,25; only one patient had hyperleukocytosis (53х109/l) at presentation.The measurement of MRD was performed in 6 patients using multiparameter flow cytometry. The measurement of MRD performed after induction therapy on the basis of megakaryocytic markers, weak CD45 expression using the initial iimmunophenotype patterns. Results Adequate measurement of the level of MRD had required extensive diagnostic immunophenotyping in order to determine the aberration of megakaryoblasts. CD9(83,3%), CD33(75%), CD34(60%), CD13(50%) apart from megakaryocyte markers (100%) were most common for blast cells in case of AMKL. The expression of CD7 antigen was as frequent as of CD117-40%. The MRD level ranged from completely negative (0%; 0.006%) to evident (1.05%). Conclusion The detection of residual tumor megakaryoblasts in AML M7 using flow cytometry is a promising method for assessing the effect of therapy. Adequate measurement of MRD requires detailed immunophenotyping in the diagnosis to determine the aberrations of megacaryoblasts immunophenotype.