Acute megakaryoblastic leukemia with t(1;22)(p13.3;q13.1); RBM15‐MKL1 mimicking hepatoblastoma in an infant: The role of karyotype in differential diagnosis

Abstract Megakaryocytes (MKs), the platelet precursors, are capable of accumulating DNA greater than a diploid content as part of their cell cycle. MKs have been recognized as mediating fibrosis in a subset of hematologic malignancies, including acute megakaryoblastic leukemia and a subset of myeloproliferative neoplasms. The mechanisms responsible for fibrosis remain only partially understood. Past studies highlighted the role of growth factors in such pathologies, and recently, the protein lysyl oxidase (LOX) has been implicated in proliferation of MKs, ploidy and deposition of fibers. LOX was initially characterized as a protein responsible for the intermolecular cross-linking of elastin and collagen, and in recent years it has been identified as regulator of various pathologies, such as cancer and inflammation. Here, we review recent advances in the understanding of the contribution of MKs to the progression of myelofibrosis, highlighting the newly identified role of LOX.

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Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome

Blood ◽

10.1182/blood-2003-05-1556 ◽

2004 ◽

Vol 103 (2) ◽

pp. 399-406 ◽

Cited By ~ 123

Author(s):

Sandeep Gurbuxani ◽

Paresh Vyas ◽

John D. Crispino

Keyword(s):

Down Syndrome ◽

High Frequency ◽

Early Event ◽

Human Leukemia ◽

Erythroid Progenitors ◽

Acute Megakaryoblastic Leukemia ◽

Future Studies ◽

Megakaryoblastic Leukemia ◽

Shed Light

Abstract GATA-1 is the founding member of a transcription factor family that regulates growth and maturation of a diverse set of tissues. GATA-1 is expressed primarily in hematopoietic cells and is essential for proper development of erythroid cells, megakaryocytes, eosinophils, and mast cells. Although loss of GATA-1 leads to differentiation arrest and apoptosis of erythroid progenitors, absence of GATA-1 promotes accumulation of immature megakaryocytes. Recently, we and others have reported that mutagenesis of GATA1 is an early event in Down syndrome (DS) leukemogenesis. Acquired mutations in GATA1 were detected in the vast majority of patients with acute megakaryoblastic leukemia (DS-AMKL) and in nearly every patient with transient myeloproliferative disorder (TMD), a “preleukemia” that may be present in as many as 10% of infants with DS. Although the precise pathway by which mutagenesis of GATA1 contributes to leukemia is unknown, these findings confirm that GATA1 plays an important role in both normal and malignant hematopoiesis. Future studies to define the mechanism that results in the high frequency of GATA1 mutations in DS and the role of altered GATA1 in TMD and DS-AMKL will shed light on the multistep pathway in human leukemia and may lead to an increased understanding of why children with DS are markedly predisposed to leukemia.

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Megakaryoblastic leukemia presenting as a temporal bone granulocytic sarcoma

Journal of Neurosurgery ◽

10.3171/jns.1993.79.1.0128 ◽

1993 ◽

Vol 79 (1) ◽

pp. 128-131 ◽

Cited By ~ 12

Author(s):

Bruce A. Kaufman ◽

Lori Jones ◽

Mary M. Zutter ◽

T. S. Park

Keyword(s):

Differential Diagnosis ◽

Surgical Treatment ◽

Temporal Bone ◽

Granulocytic Sarcoma ◽

Acute Megakaryoblastic Leukemia ◽

Content Type ◽

Megakaryoblastic Leukemia ◽

Systemic Manifestations ◽

Fine Print ◽

Neuroradiological Imaging

✓ The unusual presentation of acute megakaryoblastic leukemia as a temporal bone granulocytic sarcoma in an infant without systemic manifestations of leukemia is reviewed. Leukemia should be considered in the differential diagnosis of skull and skull-based lesions since the appearance on neuroradiological imaging is not unique in this diagnosis. Surgical treatment, as in this case, is limited to obtaining tissue for diagnosis and draining the infection.

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