Case Of Acute Megakaryoblastic Leukemia Research Articles

Acute promyelocytic leukemia with FIP1L1::RARA fusion gene: The clinical utility of transcriptome sequencing and bioinformatic analyses.

Acute promyelocytic leukemia (APL) is typically characterized by the presence of coagulopathy and the PML::RARA fusion gene. The FIP1L1::RARA has been reported as a novel fusion gene, but studies on its pathogenesis are limited. A FIP1L1::RARA fusion in a child finally diagnosed as APL was reported. RNA sequencing (RNA-seq) of six patients (three cases of acute lymphoblastic leukemia (ALL), one case of myelodysplastic syndrome (MDS), one case of acute megakaryoblastic leukemia (M7), and one case of APL with FIP1L1::RARA) were performed. Transcriptome analysis of six patients was performed by RNA-seq. The heat map was used for showing the RNA expression profile, the volcano plot for identifying differential expression genes (DEGs), and the KEGG Orthology-Based Annotation System (KOBAS) online biological information database for KEGG pathway enrichment analysis. Obvious differences between APL with FIP1L1::RARA and hematologic malignancies were identified. 1060 common differentially expressed genes (co-DEGs) were detected between APL with FIP1L1::RARA vs ALL and APL with FIP1L1::RARA vs myeloid neoplasms (MDS, M7), the up-regulated genes were mainly mapped into platelet activation, cancer, AMPK signaling pathway, PI3K-Akt signaling pathway, and MAPK signaling pathway. The down-regulated genes were significantly associated with TNF signaling pathway, Rap1 signaling pathway, Age-RAGE signaling pathway, and apoptosis. A FIP1L1::RARA fusion in a child finally diagnosed as APL was reported. RNA-seq may provide a new diagnostic method when RARA rearrangements fail to be identified by conventional methods. In the analysis of co-DEGs between case vs ALL and case vs myeloid neoplasms, the up-regulated and down-regulated genes were enriched in different signaling pathways. Further experimental studies are needed to identify pathogenesis and treatment for APL with FIP1L1::RARA.

Pediatric Acute Megakaryoblastic Leukemia with T(4;11) (Q21;Q23)/MLL-AF4 Fusion Transcript: A Case Report

Acute Megakaryoblastic Leukemia (AMKL) is a rare and biologically heterogenous subtype of Acute Myeloid Leukemia (AML) with a diverse cytogenetic profile. Mix-lineage leukemia (MLL) rearrangements are commonly found in infant Acute Lymphoblastic Leukemia (ALL) and childhood AML. However, the occurrence of MLL rearrangements in AMKL is very rare. Here, we report a pediatric case of AMKL with MLL- AF4 fusion derived from t(4;11) (q21;q23). To our knowledge, the case has not been reported from China. Our observation supports understanding of molecular diversity in AMKL. The varying molecular features of AMKL are warranted to fully understand to develop novel therapeutic strategies.

A rare case of acute megakaryoblastic leukemia with orbital chloroma in a non-Down syndrome child

Acute megakaryoblastic leukemia (AMKL) is a rare disease accounting for 7%–10% of acute myeloid leukemia (AML) in children. It is uncommon in children without Down syndrome (DS). Orbital chloroma is usually associated with AML M2, M4, and M5. Herein, we report the case of a 22-month-old female who was diagnosed to have AMKL with orbital chloromas and without DS. Morphology and the initial panel of immunophenotyping were inconclusive and the presence of orbital chloromas added to the ambiguity. The presence of CD61 expression and marrow fibrosis supported by hyperdiploidy helped us clinch the diagnosis. Hence, comprehensive analysis of morphology, immunophenotyping, and cytogenetics is warranted to make an accurate diagnosis of AMKL.

Hemophagocytosis by Leukemic Megakaryoblasts in Acute Myeloid Leukemia (Megakaryoblastic) With t(1;22)(p13;q13);RBM15-MKL1

Acute megakaryoblastic leukemia is a rare variant of acute myeloid leukemia, whereby leukemic blasts display characteristic morphologic and phenotypic features indicating megakaryocytoid differentiation. A distinct entity characterized by the t(1;22)(p13;q13) translocation, resulting in the RBM15-MKL1 fusion oncogene, has been recently recognized. This is predominantly a disease afflicting infants and displays characteristic clinical features. We present a case of acute megakaryoblastic leukemia with t(1;22)(p13;q13) along with a discussion of the current understanding of the molecular biology of RBM15-MKL1. This case also displayed striking and unusual morphologic appearances including extensive hemophagocytosis by leukemic blasts, which has not been previously reported for this particular type of leukemia.

Clinicopathological Characteristics of Extramedullary Acute Megakaryoblastic Leukemia (AMKL): Report of a Case with Initial Mastoid Presentation and Review of Literature to Compare Extramedullary AMKL and Non-AMKL Cases

Extramedullary acute megakaryoblastic leukemia (AMKL) is a rare neoplasm with a varied clinical presentation. AMKL with initial mastoid presentation has never been reported. The extreme rarity of mastoid AMKL, together with the tendency of extramedullary AMKL to mimic other small blue cell tumors, can create a diagnostic challenge. We report a case of AMKL that initially presented as a mastoid lesion and provide a comprehensive review and analysis that compares the characteristics of extramedullary AMKL and nonmegakaryoblastic acute myeloid leukemia (AML) in reported pediatric cases over the past 30 years. We found that patients with extramedullary AMKL were not only younger than patients without megakaryocytic differentiation but were also limited to those ≤ 2 years of age. In addition, girls predominated in both AMKL and AML MLL(+) groups compared with other types of AML (P = 0.0366 and P = 0.0082). Furthermore, we found that extramedullary AMKL was more likely to involve bone than AML MLL(+) (P < 0.0001) or other types of AML (P = 0.0002). These findings suggest that extramedullary AMKL should be considered in the differential diagnosis of SBCT in children, especially in patients with mastoid or other bony lesions, those ≤ 2 years of age, and female patients.

Mosaic trisomy 21 and trisomy 14 as acquired cytogenetic abnormalities without GATA1 mutation in a pediatric non-down syndrome acute megakaryoblastic leukemia

One case of acute megakaryoblastic leukemia (AMKL) with trisomy 21, trisomy 14 and unmutated GATA1 gene in a phenotypically normal girl was reported. The patient experienced transient myelodysplasia before the onset of AMKL. The bone marrow blasts manifested typical morphology of megakaryoblast both by the May-Giemsa staining and under the electronic microscopy. Leukemic cells were positive for CD13, CD33, CD117, CD56, CD38, CD41 and CD61 in flow cytometry analysis. Cytogenetic study showed karyotype of 48, XX, +14, +21 in 40% metaphases. Known mutations of GATA1 gene in Down syndrome or acquired trisomy 21 were not detected in this case.

Acute megakaryoblastic leukemia in a child with the MLL‐AF4 fusion gene

Mixed-lineage leukemia (MLL) rearrangements are commonly observed in childhood acute lymphoblastic and myeloid leukemia, as well as therapy-related leukemia. However, the occurrence of MLL rearrangements in acute megakaryoblastic leukemia (AMKL) is very rare. We report a pediatric case of AMKL with the MLL-AF4 fusion transcript. MLL-AF4 is derived from t(4;11)(q21:q23) and occurs exclusively in B-cell lineage leukemia. To our knowledge, MLL-AF4 as well as t(4;11)(q21:q23) has not been reported in adult and childhood AMKL. Thus, our case provides new insight into the molecular mechanisms of MLL-AF4-associated leukemia.

Hemophagocytosis by leukemic blasts in 7 acute myeloid leukemia cases with t(16;21)(p11;q22)

In a previous study of a case of acute megakaryoblastic leukemia with t(16;21)(p11;q22), which displayed hemophagocytosis by leukemic blasts, the authors mentioned that the same type of morphology had been cited in the literature for 4 other cases of acute myeloid leukemia (AML) with the same translocation. This observation prompted the authors to examine more cases of AML with t(16;21)(p11;q22) for this morphology. The authors reviewed bone marrow smears for the presence of hemophagocytosis in 7 patients with AML identified as having t(16;21)(p11;q22). The leukemias belonged to the FAB-M1/M7 (n = 5), M5b (n = 2), and contained phagocytic blasts in various percentages (< 0.2-36.7%). The blasts contained either single or multiple cytoplasmic vacuoles, in some of which the phagosomes were visible. The engulfed hemopoietic cells (red cells, erythroblasts, lymphocytes, and thrombocytes) were also noted in their cytoplasm. These observations confirmed that hemophagocytosis by leukemic blasts is a common and characteristic feature of this type of leukemia. The study of 12 cases (the 7 cases described here and the previous 5 cases) strongly supports the hypothesis that hemophagocytosis by leukemic blasts is common and characteristic in this type of leukemia, which may be related to the specific chromosome aberration of t(16;21)(p11;q22).

Characteristics of a Cell Line Established from a Case of Acute Megakaryoblastic Leukemia

Acute megakaryoblastic leukemia is uncommon and comprises about 5% of acute nonlymphoid leukemias in the French-American-British classification. Cell lines from such leukemias are relatively rare with only about 8 reported in the literature. We established a cell line from a case of acute megakaryoblastic leukemia arising in a 2-year-old child. Surface marker studies of the cells confirmed their megakaryoblastic nature, with 54% of the cells being CD61 positive and peroxidase and esterase negative. The cells had a doubling time of 72 h. Emperipolesis (a phenomenon in which a cell, usually a lymphocyte or neutrophil, enters another cell, moves about and leaves without undergoing phagocytosis) of one blast into another, larger one, was occasionally seen, and a review of the original bone marrow specimen also showed emperipolesis of neutrophils into the megakaryoblasts. The cells responded to interleukin 3 and were inhibited with all-trans-retinoic acid. The karyotype of the cells was the 46,XX,-16 with a marker chromosome. The marker chromosome is possibly chromosome 16 with a small segment of a chromosome translocated to the terminal portion of chromosome 16.

Severe Hypercalcemia in a Child with Relapsed Megakaryoblastic Leukemia: Report of a Case and Review of the Literature

Severe Hypercalcemia in a Child with Relapsed Megakaryoblastic Leukemia: Report of a Case and Review of the Literature

Acute megakaryoblastic leukemia in Down syndrome, following thrombocytopenia with antiplatelet antibody.

We report a case of acute megakaryoblastic leukemia (AMKL) with antiplatelet antibody in a boy with Down syndrome. When the patient was admitted, his platelet count was 1.3 X 10(4)/mm3 and antiplatelet antibody in the plasma was detected. Two months after admission, blasts, which showed positive reaction to both antiplatelet monoclonal antibody and platelet peroxidase, increased.

Myeloperoxidase-Positive Acute Megakaryoblastic Leukemia

Acute megakaryoblastic leukemia (FABM7) is an unusual but well recognized form of acute myelogenous leukemia in which the bone marrow blast cells are phenotypically recognized by the demonstration of cytoplasmic platelet peroxidase or surface staining for the IIb/IIIa platelet-specific glycoprotein. Herein, the authors report a case of acute megakaryoblastic leukemia that satisfies the accepted French-American-British criteria and in which the blast cells also exhibit evidence of myeloid differentiation, including surface MY7 (CD13) by flow cytometry and immunocytochemical positivity for myeloperoxidase. These findings suggest that megakaryoblasts may be closely related to myelomonoblasts, that they have the potential to partially differentiate along multiple phenotypic lines, and that aberrant phenotypes can occur that do not correspond to known stages of normal maturation. The authors illustrate the difficulty in classification of these aberrant phenotypes by standard cytochemical and morphologic criteria.

A Case of Acute Megakaryoblastic Leukemia in Childhood

A Case of Acute Megakaryoblastic Leukemia in Childhood

MEGAKARYOCYTIC REACTION LOCALIZED IN THE BONE MARROW

HITHERTO there have been only two diseases known in which he megakaryocytes occupy the center of the pathologic picture. One is thrombopenic purpura, in which these cells suffer an injury. The other is chronic aleukemic myelosis, characterized by an extramedullary megakaryopoiesis. A case of acute megakaryoblastic leukemia, the only one so far recorded in the literature, was described by von Boros. 1 However, its authenticity is doubted by some hematologists. 2 In other lesions in which these bone marrow cells are involved, such as in chronic myeloid leukemia, hyperthyroidism and polycythemia, they merely play a secondary role. In the present case the megakaryocytes were the elements affected principally and in a manner unique in hematologic history. It is reported, also, because of the light it throws on the problems concerning the origin and maturation of megakaryocytes and the derivation of platelets from them. REPORT OF A CASE G. M., a