Acute megakaryocytic leukemia: What have we learned

Hahn, Andrew W.; Li, Bojia; Prouet, Philippe; Giri, Smith; Pathak, Ranjan; Martin, Michael

doi:10.1016/j.blre.2015.07.005

Cited by 27 publications

(25 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The initial pathologic diagnosis of both the AML M7 and GCT were difficult. The pathologic interpretation of the diagnostic bone marrow biopsy was complicated by marrow fibrosis and numerous background histiocytes (not uncommon in AML M7) and moderate crush artifact ( Hahn et al 2015 ). Although the case did not meet the World Health Organization (WHO) guidelines for a diagnosis of AML with >20% blasts, the aspirate with 15% blasts was hemodilute, and the overall findings were consistent with a diagnosis of AML M7 ( Vardiman et al 2002 ).…”

Section: Resultsmentioning

confidence: 99%

A common founding clone with TP53 and PTEN mutations gives rise to a concurrent germ cell tumor and acute megakaryoblastic leukemia

Riedell

Miller

et al. 2016

Cold Spring Harb Mol Case Stud

View full text Add to dashboard Cite

We report the findings from a patient who presented with a concurrent mediastinal germ cell tumor (GCT) and acute myeloid leukemia (AML). Bone marrow pathology was consistent with a diagnosis of acute megakaryoblastic leukemia (AML M7), and biopsy of an anterior mediastinal mass was consistent with a nonseminomatous GCT. Prior studies have described associations between hematological malignancies, including AML M7 and nonseminomatous GCTs, and it was recently suggested that a common founding clone initiated both cancers. We performed enhanced exome sequencing on the GCT and the AML M7 from our patient to define the clonal relationship between the two cancers. We found that both samples contained somatic mutations in PTEN (C136R missense) and TP53 (R213 frameshift). The mutations in PTEN and TP53 were present at ∼100% variant allele frequency (VAF) in both tumors. In addition, we detected and validated five other shared somatic mutations. The copy-number analysis of the AML exome data revealed an amplification of Chromosome 12p. We also identified a heterozygous germline variant in FANCA (S858R), which is known to be associated with Fanconi anemia but is of uncertain significance here. In summary, our data not only support a common founding clone for these cancers but also suggest that a specific set of distinct genomic alterations (in PTEN and TP53) underlies the rare association between GCT and AML. This association is likely linked to the treatment resistance and extremely poor outcome of these patients. We cannot resolve the clonal evolution of these tumors given limitations of our data.

show abstract

Section: Resultsmentioning

confidence: 99%

A common founding clone with TP53 and PTEN mutations gives rise to a concurrent germ cell tumor and acute megakaryoblastic leukemia

Riedell

Miller

et al. 2016

Cold Spring Harb Mol Case Stud

View full text Add to dashboard Cite

show abstract

“…Sagittal (D) T1 post gadolinium enhanced image shows reduced range of lesion than before. Discussion: Acute megakaryocytic leukemia is a rare subtype of acute myeloid leukemia (AML) caused by primitive megakaryoblasts arrested at a certain stage of differentiation and proliferated abnormally [1]. Clinical symptoms were similar in many respects to those observed in patients with other types of acute leukemia and included progressive pallor, bleeding, bone pain and palpable liver.…”

Section: Figure42 Intermediate A-dmentioning

confidence: 99%

Multiple Malignant Meningiomas Presenting As Thrombocytopenia

2019

JCRC

View full text Add to dashboard Cite

Backgrounds: Malignant meningiomas are CNS tumors arising from the arachnoids cap cells of the meninges, very rare in infants. Clinically, intracranial hypertension or focal neurological deficits are usually seen for mass effect, rather than leukemoid symptoms. Methods: Retrospectively analyze the detailed clinical development, diagnosis and treatment of a 10-month-old boy initially hospitalized due to leukemoid symptoms. After careful examination, malignant meningioma (WHO grade III) was proved by the biopsy and histopathology. Chemotherapy (three cycle of ifosfamide 100 mg/kg for 3 days, plus doxorubicin 1 mg/ kg for 2 days every 21 days) in combination with imatinib. Results: Dura nodules significantly reduced in size, skin bleeding spots, thrombocytopenia and enlarged superficial lymph almost disappeared. Conclusion: This study was conducted to demonstrate dynamic changes after effective individualized treatment. Meanwhile, we proposed that the invasiveness of meningioma induces somatic DNA damage, leading to abnormal platelet production and megakaryocytic morphology.

show abstract

“…Acute megakaryoblastic myeloid leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML) that presents different genetic characteristics and morphological phenotypes. AMKL appears frequently in childhood but is also common in adults in their 50s or 60s [55]. Some cases are developed after chemotherapy or are the result of leukemic transformation of chronic myeloproliferative neoplasms [56].…”

Section: Jak2t875n Mutation In Acute Megakaryoblastic Myeloid Leukemiamentioning

confidence: 99%

“…Diverse cytogenic abnormalities are associated to AMKL that differs between children and adults. The most commonly seen aberrations in adulthood are inv(3)(q21;q26), deletions of chromosomes 5 and 7, and t(9;22)(q34;q11) [55]. Children that develop JAK, an Oncokinase in Hematological Cancer DOI: http://dx.doi.org /10.5772/intechopen.84177 this disease are subdivided in two groups.…”

Section: Jak2t875n Mutation In Acute Megakaryoblastic Myeloid Leukemiamentioning

confidence: 99%

JAK, an Oncokinase in Hematological Cancer

Recio¹,

Aranda-Tavío²,

Guerra-Rodríguez³

et al. 2019

Tyrosine Kinases as Druggable Targets in Cancer

View full text Add to dashboard Cite

Janus kinases (JAKs) play an essential role in the regulation of cytokine signaling. They control cell survival, proliferation, differentiation, immune response, and hematopoiesis. Deregulation of JAK signaling has been associated to the pathogenesis of numerous immune-inflammatory diseases, hematological malignancies, and solid tumors. Thus, JAK proteins have emerged as attractive therapeutic targets in the last decade. The discovery of the gain-of-function JAK2 mutation (JAK2 V617F) as the main cause of polycythemia vera-a chronic myeloproliferative syndromeled to the development of the JAK inhibitor ruxolitinib. This key finding opened the door to the search for new therapeutic agents able to suppress the constitutive activation of JAK signaling in hematological cancers and other tumors. However, given the conserved nature of the kinase domain among JAK family members, and the interrelated roles of JAK kinases in many physiological processes, including hematopoiesis and immunity, the broad usage of JAK inhibitors in hematology is challenged by their narrow therapeutic window. Novel therapies are, therefore, needed. This chapter focuses on the understanding of the complex signaling of JAK proteins in cancerous cells, the various JAK aberrations implicated in myeloproliferative neoplasms, leukemia, and lymphoma, and the clinically available JAK inhibitors in cancer therapy.

show abstract

Acute megakaryocytic leukemia: What have we learned

Cited by 27 publications

References 61 publications

A common founding clone with TP53 and PTEN mutations gives rise to a concurrent germ cell tumor and acute megakaryoblastic leukemia

A common founding clone with TP53 and PTEN mutations gives rise to a concurrent germ cell tumor and acute megakaryoblastic leukemia

Multiple Malignant Meningiomas Presenting As Thrombocytopenia

JAK, an Oncokinase in Hematological Cancer

Contact Info

Product

Resources

About