Acute Megakaryoblastic Leukemia Research Articles

Cases of transient abnormal myelopoiesis

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.

Exposure of Patient-Derived Mesenchymal Stromal Cells to TGFB1 Supports Fibrosis Induction in a Pediatric Acute Megakaryoblastic Leukemia Model.

Bone marrow fibrosis (BMF) is a rare complication in acute leukemia. In pediatrics, it predominantly occurs in acute megakaryoblastic leukemia (AMKL) and especially in patients with trisomy 21, called myeloid leukemia in Down syndrome (ML-DS). Defects in mesenchymal stromal cells (MSC) and cytokines specifically released by the myeloid blasts are thought to be the main drivers of fibrosis in the bone marrow niche (BMN). To model the BMN of pediatric patients with AMKL in mice, we first established MSCs from pediatric patients with AMKL (n = 5) and ML-DS (n = 9). Healthy donor control MSCs (n = 6) were generated from unaffected children and adolescents ≤18 years of age. Steady-state analyses of the MSCs revealed that patient-derived MSCs exhibited decreased adipogenic differentiation potential and enrichment of proliferation-associated genes. Importantly, TGFB1 exposure in vitro promoted early profibrotic changes in all three MSC entities. To study BMF induction for longer periods of time, we created an in vivo humanized artificial BMN subcutaneously in immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice, using a mixture of MSCs, human umbilical vein endothelial cell, and Matrigel. Injection of AMKL blasts as producers of TGFB1 into this BMN after 8 weeks induced fibrosis grade I/II in a dose-dependent fashion over a time period of 4 weeks. Thus, our study developed a humanized mouse model that will be instrumental to specifically examine leukemogenesis and therapeutic targets for AMKL blasts in future. IMPLICATIONS: TGFB1 supports fibrosis induction in a pediatric AMKL model generated with patient-derived MSCs. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/18/10/1603/F1.large.jpg.

Loss of Normal Polyploid Spectrum as Marker of Clonality in Acute Megakaryoblastic Leukemia Evolving from Pre-Existing Primary Myelofibrosis.

Loss of Normal Polyploid Spectrum as Marker of Clonality in Acute Megakaryoblastic Leukemia Evolving from Pre-Existing Primary Myelofibrosis.

Utility of CD36 as a novel addition to the immunophenotypic signature of RAM-phenotype acute myeloid leukemia and study of its clinicopathological characteristics.

In 2016, Children Oncology Group (COG) described a new high-risk subtype of acute myeloid leukemia (AML) with a distinct immunophenotypic-signature, RAM-phenotype (RAM-AML). Data on clinical and laboratory features of RAM-AML are still limited to COG report only. Herein, we report the clinicopathological characteristics and detailed immunophenotypic features of RAM-AML patients. In COG report, 38% of RAM-AML belonged to acute megakaryoblastic leukemia (AMKL)-subtype. Hence, we further compared the immunophenotypic features RAM-AML with non-RAM-AMKL diagnosed during the same study period. We included RAM-AML and non-RAM AMKL patients diagnosed between January 2017 and December 2019. We studied their morphological, cytochemical, immunophenotyping, cytogenetic, and molecular characteristics. Mean fluorescent intensity (MFI) and expression-pattern of immunophenotypic markers of RAM-AML were compared with non-RAM AMKLs patients. We identified 11 RAM-AML (1%) and 21 non-RAM AMKL (1.9%) patients in 1102 pediatric-AML patients. Seven of 11 (63.64%) patients belonged to FAB-M7-subtype. CD56, CD117, and CD33 demonstrated overexpression, whereas CD45 and CD38 showed under-expression in RAM-AML patients. CD36 was consistently negative in RAM-AML, whereas moderate-bright positive in non-RAM AMKLs patients (p < 0.0001). On principle component analysis, addition of CD36 enhanced the visual-separation between RAM-AML and non-RAM AMKL clusters. Cytogenetic and molecular studies did not show any recurrent abnormality; however, RNA-sequencing study revealed CBFA2T3-GLIS2-fusion in three of seven (42.8%) RAM-AML patients. We report the clinicopathological characteristics and the detailed immunophenotypic profile in the world's second series of RAM-AML patients. We further report a novel finding of CD36-negative expression as an additional parameter to the multidimensional immunophenotypic signature of this entity.

Downregulation of MIR100HG Induces Apoptosis in Human Megakaryoblastic Leukemia Cells.

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.

Acute promyelocytic leukemia in a child with reticulin fibrosis

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.

Abstract B34: Cord blood CD34+ HSPCs: An in vitro model system for characterizing NUP98 fusions

Abstract Chromosomal translocations of the Nucleoporin 98 gene (NUP98) are associated with multiple hematopoietic malignancies. In particular, NUP98 rearrangements can be found in up to 6.6% of de novo cases of pediatric AML. Specific subpopulations of pediatric AML appear to be even more enriched for NUP98 fusions, with over 16% of cytogenetically normal pediatric AML patients and 15% of non-Down syndrome acute megakaryoblastic leukemia (AMKL) patients harboring these fusions. Clinically, the NUP98-KDM5A fusion is associated with erythroid and megakaryocytic leukemias while the NUP98-NSD1 fusion is associated with myelomonocytic leukemias. When NUP98 fusions are present in AML, they confer a poor prognosis. To better characterize the role of these fusions in human hematopoiesis, we used cord blood CD34+ (cb-CD34+) hematopoietic stem and progenitor cells (HSPCs) as an in vitro model system. We transduced cb-CD34+ HSPCs with NUP98-NSD1, NUP98-KDM5A, or empty vector control and studied the effects on cell proliferation and differentiation in liquid culture media containing cytokines (IL-6, FLT3-Ligand, SCF, TPO, and SR1 (an aryl hydrocarbon receptor antagonist)). NUP98-NSD1 and NUP98-KDM5A fusions increase the proliferation rate in liquid culture by three-fold and 19-fold, respectively (p&amp;lt;0.05). Consistent with observations from patients with these fusions, cells expressing NUP98-KDM5A have increased expression of CD235A and CD71, consistent with erythroid differentiation (p&amp;lt;0.05). In addition, cells expressing NUP98-NSD1 have increased expression of CD11b compared to NUP98-KDM5A (p&amp;lt;0.01) expressing cells. When placed in methylcellulose, the NUP98 fusions tested had no effect on total colony number, but we observed more erythroid differentiation for NUP98-KDM5A compared to vector control (p&amp;lt;0.05). Overall, the results of these in vitro studies demonstrate increased proliferation and inhibition of differentiation in HSPCs by NUP98 fusions, and cell differentiation patterns parallel the different AML subtypes observed in patients with NUP98-NSD1 and NUP98-KDM5A fusions. We propose cbCD34+ HSPCs as a promising system for in vitro modeling of NUP98 fusions. Citation Format: Ryan Hiltenbrand, Jonathan Miller, Jeffery Klco. Cord blood CD34+ HSPCs: An in vitro model system for characterizing NUP98 fusions [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B34.

Clinical Characteristics and Prognosis of 27 Patients with Childhood Acute Megakaryoblastic Leukemia.

BackgroundThe aim of this study was to investigate the clinical features and prognostic factors of childhood acute megakaryoblastic leukemia (AMKL).Material/MethodsThe data of 27 cases of childhood AMKL admitted from November 2009 to July 2018 were retrospectively analyzed. The survival analysis and prognostic factors were analyzed by Kaplan-Meier method.ResultsThe median follow-up time was 26.4 months in 27 cases, and the complete response rate was 92.31% after 2 chemotherapy courses. Eight patients underwent bone marrow transplantation after 3–6 courses. Five patients died after transplantation, 4 of whom died due to recurrence after transplantation. Of the 27 patients, 10 developed recurrence (37.04%), and 8/10 had recurrence within 1 year. The 3-year overall survival rate and disease-free survival rates were (47±12)% and (36±14)%, respectively. Of the 27 AMKL cases, the 3 with Down syndrome (DS-AMKL) all survived after treatment, and the 3-year overall survival rate was 100%. However, of the other 24 AMKL patients without Down syndrome (non-DS-AMKL), 6 died and 6 abandoned treatment, and the 3-year overall survival rate was only 50%. Univariate analysis showed that 3-year overall survival rate was not correlated to gender, age, number of newly diagnosed white blood cells, karyotype, remission after 2 courses of treatment, and transplant after 3 courses of treatment of childhood AMKL cases. Nevertheless, recurrence and remission after 2 courses of treatment were significantly correlated with 3-year overall survival rate.ConclusionsChildren with non-DS-AMKL have a high degree of malignancy and are prone to early recurrence with a poor prognosis, whereas the prognosis of DS-AMKL is relatively good. Recurrence after treatment and remission after 2 courses of treatment are important factors influencing the prognosis of childhood AMKL. Recurrence after transplantation is the leading cause of death in transplantation patients.

Abstract B03: Acute megakaryoblastic leukemia is associated with poor overall survival and enriched in JAK2 variants

Abstract In this study, we aimed to characterize the molecular mechanisms of two very rare subtypes of AML: acute megakaryoblastic leukemia (AMKL) and acute panmyelosis with myelofibrosis (APMF). Our goal is to describe the clinical-pathologic features of APMF and explore the genomic landscape AMKL to further understand these rare malignancies. We identified 35 patients diagnosed with AMKL (n=27) and APMF (n=8) at Mayo Clinic between 1995 and 2015 by retrospective chart review. For 10 of the AMKL patients, tissue was available for whole-exome sequencing and was analyzed in comparison to a published AML reference population. The median overall survival was shorter in patients with AMKL (3.9 months, 95% CI 1.7-7.4) than in patients with APMF (14.3 months, 95% CI 0.7-NE, p = 0.026,). For both AMKL and APMF, patients who underwent allogeneic hematopoietic stem cell transplantation had better overall survival (14.3 months, 95% CI 1.9-NE) compared to those not undergoing transplantation (4.6 months, 95% CI 1.5-7.4, p = 0.003). Patients with AMKL presented more frequently with splenomegaly, with higher peripheral blood blast counts, and with higher serum lactate dehydrogenase concentrations. 9 out of 10 AMKL patients with available tissue for sequencing demonstrated variants in 22 of 35 AML driver genes, with JAK2 V617F as the most common mutation. Although our small study numbers preclude firm conclusions, it does reflect the rarity of these AML subtypes. Furthermore, inferior survival in AMKL (compared to APMF) was reflected in its proliferative disease features such as splenomegaly, high blast counts, and high lactate dehydrogenase. Interestingly, the presence of JAK2 V617F variants in 40% of the interrogated samples was higher than expected. Although JAK2 is a known molecular driver in myeloproliferative neoplasms, it is actually very rare in de novo AML (~1%). Despite improved survival with allogeneic stem cell transplant, we can conclude that treatment outcomes for AMKL and APMF with standard-of-care therapy were sobering and that patients with these rare AML subtypes should undergo molecular evaluation to qualify them for clinical trials with novel targeted therapies. Citation Format: Marissa Li, Moritz Binder, Basma Basha, Ben Zhang, Alejandro Ferrer, Yuanhan Liu, Mrinal Patnaik, David Viswanatha, Naseema Gangat. Acute megakaryoblastic leukemia is associated with poor overall survival and enriched in JAK2 variants [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B03.

Platelet morphology

Abstract Background The examination of a peripheral blood smear is mandatory in case of unexplained thrombocytopenia or thrombocytosis. First, the number of platelets should be estimated in order to confirm the platelet count determined by the haematology analyser, and to rule out causes of spuriously low or elevated platelet counts. Second, the size and morphological features of the platelets, which may provide information on the underlying cause of the low or enhanced platelet count, have to be assessed. Content This review summarizes the physiological and pathological features of platelet size and morphology, circulating megakaryocytes, micromegakaryocytes and megakaryoblasts, and provides an overview of current guidelines on the reporting of platelet morphology. Summary In the diagnostic work-up of a patient with thrombocytopenia, the size of the platelets is of diagnostic relevance. Thrombocytopenia with small platelets is suggestive of a defect in platelet production, whereas the presence of large platelets is more likely to be associated with enhanced platelet turnover or hereditary thrombocytopenias. Morphological platelet abnormalities may affect the granulation and the shape and are frequently associated with abnormalities of platelet size. Platelet anomalies can be found in various haematologic disorders, such as myelodysplastic syndromes, myeloproliferative neoplasms, acute megakaryoblastic leukaemia or hereditary thrombocytopenias.

BMP2K dysregulation promotes abnormal megakaryopoiesis in acute megakaryoblastic leukemia

BackgroundForced 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.ResultsBMP2K 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.ConclusionsBMP2K 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.

Efficacy and safety of reduced-intensity chemotherapy in children with Down syndrome-related myeloid leukemia

Objective To investigate the efficacy and safety of reduced-intensity chemotherapy in treatment of children with Down syndrome-related myeloid leukemia (ML-DS). Methods The clinical data of 3 hospitalized children with ML-DS who were diagnosed and treated by Children Oncology Group Trial A2971 chemotherapy regimen in Fujian Medical University Union Hospital from January 2016 to June 2019 were retrospectively analyzed, and the clinical characteristics, efficacy and safety were summarized. Results The ages of 3 children were 1 year and 6 months, 2 years and 6 months, and 1 year and 10 months. Two cases were acute monocytic leukemia, and 1 case was acute megakaryoblastic leukemia. Two cases were positive for EVI1 gene and 1 case had ASXL1 gene mutation, and all 3 cases had complex karyotype. After one course of induction chemotherapy, all 3 cases achieved complete remission, and the minimal residual disease turned negative. During the induction chemotherapy, all 3 cases had severe myelosuppression, and 2 cases of them suffered from severe pneumonia and 1 case of them suffered from intestinal infection and septic shock. Conclusion The efficacy of reduced-intensity chemotherapy in children with ML-DS is favorable, but the severe complications such as myelosuppression and infection need to be taken seriously. Key words: Leukemia, myeloid, acute; Down syndrome; Antineoplastic combined chemotherapy protocols

Metastatic germ cell tumour presenting as acute megakaryoblastic leukaemia and disseminated melanoma: A case report

Since first recognised in 1985, studies have described the unique and rare association between haematological malignancies and germ cell tumours, most commonly acute megakaryoblastic leukemia (AMKL) and non-seminomatous germ cell tumours. A recent molecular study identified mutations in PTEN and TP53 in both tumours, supporting the theory that distinct genomic alterations underlie this rare association. It is also recognised that teratomatous components of mediastinal germ cell tumours have a tendency for secondary transformation to other malignancies including melanoma. We report a case of a 38-year-old man presenting with severe back pain. An MRI spine demonstrated diffuse marrow replacement and bony lesions concerning for metastatic disease. The patient had recently completed chemotherapy for a mediastinal germ cell tumour with teratomatous components on histopathology. A staging CT identified liver and splenic lesions suspicious for metastatic deposits. A peripheral blood film performed on admission was found to have circulating blasts with an immunophenotype consistent with megakaryoblasts. He subsequently underwent a bone marrow biopsy confirming AMKL with a TP53 mutation. A liver biopsy revealed necrotic tumour with immunohistochemistry consistent with metastatic melanoma. In summary, we describe a case of treated mediastinal germ cell tumour with secondary transformation to metastatic melanoma with synchronous AMKL.

A retrospective study of myeloid leukaemia in children with Down syndrome in Ireland.

Acute megakaryoblastic leukaemia (AMKL) is a subtype of myeloid leukaemia and is the most common leukaemia type in children with Down syndrome (DS) under 4years of age. AMKL is often preceded by a transient neonatal pre-leukaemic syndrome, transient myeloproliferative disorder (TMD). Although TMD often spontaneously resolves, 20-30% of these patients subsequently develop AMKL within the first 4years of life. To perform a retrospective consecutive national audit of all documented cases of childhood TMD and AMKL-DS from 1990 to 2018 at Our Lady's Children's Hospital, Crumlin (OLCHC), Ireland. All patients with a diagnosis of AMKL treated consecutively at (OLCHC) between 1990 and 2018 were reviewed. Kaplan-Meier survival curves were constructed. Twenty-seven patients with AMKL-DS were identified. A prior neonatal diagnosis of TMD was described in 10 patients (37%). Nineteen patients (70%) are alive and well, in complete remission, at a median follow-up of 11.4years. Overall survival (OS) of this cohort has risen from 54% from those treated between the years 1990 and 2004 (n = 13) to 93% for those treated between the years 2005 and 2018 (n = 14). High cure rates are observed in AMKL-DS using current polychemotherapy protocols. The finding of a low platelet count at time of diagnosis is in keeping with the knowledge that AMKL-DS is a malignancy of platelet progenitor cells.

Retraction Note: Blockage of miR-92a-3p with locked nucleic acid induces apoptosis and prevents cell proliferation in human acute megakaryoblastic leukemia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

TP53 and PTEN mutations were shared in concurrent germ cell tumor and acute megakaryoblastic leukemia

BackgroundThe 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.MethodsWe 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.ResultsSixteen 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.ConclusionsAll 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.

A rare case of therapy-associated acute megakaryoblastic leukemia

A rare case of therapy-associated acute megakaryoblastic leukemia

The Pediatric Acute Leukemia Fusion Oncogene ETO2‐GLIS2 Increases Self‐Renewal and Alters Differentiation in a Human Induced Pluripotent Stem Cells‐Derived Model

Supplemental Digital Content is available in the text.

Ontogenic Changes in Hematopoietic Hierarchy Determine Pediatric Specificity and Disease Phenotype in Fusion Oncogene-Driven Myeloid Leukemia.

Fusion oncogenes are prevalent in several pediatric cancers, yet little is known about the specific associations between age and phenotype. We observed that fusion oncogenes, such as ETO2-GLIS2, are associated with acute megakaryoblastic or other myeloid leukemia subtypes in an age-dependent manner. Analysis of a novel inducible transgenic mouse model showed that ETO2-GLIS2 expression in fetal hematopoietic stem cells induced rapid megakaryoblastic leukemia whereas expression in adult bone marrow hematopoietic stem cells resulted in a shift toward myeloid transformation with a strikingly delayed in vivo leukemogenic potential. Chromatin accessibility and single-cell transcriptome analyses indicate ontogeny-dependent intrinsic and ETO2-GLIS2-induced differences in the activities of key transcription factors, including ERG, SPI1, GATA1, and CEBPA. Importantly, switching off the fusion oncogene restored terminal differentiation of the leukemic blasts. Together, these data show that aggressiveness and phenotypes in pediatric acute myeloid leukemia result from an ontogeny-related differential susceptibility to transformation by fusion oncogenes. SIGNIFICANCE: This work demonstrates that the clinical phenotype of pediatric acute myeloid leukemia is determined by ontogeny-dependent susceptibility for transformation by oncogenic fusion genes. The phenotype is maintained by potentially reversible alteration of key transcription factors, indicating that targeting of the fusions may overcome the differentiation blockage and revert the leukemic state.See related commentary by Cruz Hernandez and Vyas, p. 1653.This article is highlighted in the In This Issue feature, p. 1631.

A case of neonatal acute megakaryoblastic leukemia that was difficult to differentiate from transient abnormal myelopoiesis

A case of neonatal acute megakaryoblastic leukemia that was difficult to differentiate from transient abnormal myelopoiesis