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Mutational analysis of candidate tumor-associated genes in acute megakaryoblastic leukemia

Leukemia volume 23, pages 2159–2160 (2009)Cite this article

Acute megakaryoblastic leukemia (AMKL) is a biologically and cytogenetically heterogeneous subtype of acute myeloid leukemia. AMKL either presents de novo or as therapy-related leukemia after chemotherapy or as a leukemic transformation of chronic myeloproliferative neoplasms. The incidence of AMKL in adult de novo acute myeloid leukemia patients is estimated to be about 1–2%, whereas the incidence in the pediatric population is as high as 5–7%, largely because of its association with Down's syndrome (DS).1, 2 DS-AMKL and non-DS-AMKL have vastly different genetic abnormalities and outcomes. Although patients with DS-AMKL have a favorable prognosis, with a 5-year event-free survival rate between 70 and 80%, children with non-DS-AMKL fare much worse, with a 5-year event-free survival of 22–28%.2, 3 Similarly, the prognosis of adult AMKL is dismal, with a median survival of ∼10 months.1

With respect to the molecular basis for megakaryocytic subtypes of acute myeloid leukemia, DS-AMKL blasts uniformly harbor trisomy 21 and somatic mutations in the X-linked hematopoietic transcription factor, GATA1.4 Distinct abnormalities, such as t(1;22)(p13;q13), which leads to expression of the OTT-MAL (RBM15-MLK1) fusion protein, t(10;11), t(9;11) or +8 are seen in cases of non-DS pediatric AMKL.4 However, very little is known about the etiology of adult AMKL, as no specific chromosomal rearrangements or genetic mutations have been described, apart from a rare detection of mutations in c-MPL, c-KIT, JAK2, JAK3 or FLT3.4, 5, 6

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Acknowledgements

The authors thank the Eastern Cooperative Group (ECOG) and Children's Oncology Group (COG) for contributing specimens to this study. DS-AMKL and TMD samples from study COG A2971 were supported by the National Cancer Institute Grant nos U10 CA98543 and U10 CA98413. This work was also supported in part by the National Cancer Institute Grant no CA101774 to JDC.

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Author notes

  1. R Bhat and S Malinge: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology-Oncology, Children's Memorial Hospital, Chicago, IL, USA

    R Bhat

  2. Department of Medicine, Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    R Bhat, S Malinge, M S Tallman & J D Crispino

  3. Division of Hematology/Oncology/Bone Marrow Transplantation, Children's Mercy Hospital and Clinics, Kansas City, MO, USA

    A S Gamis

  4. Department of Clinical Cancer Genetics, City of Hope National Medical Center, Duarte, CA, USA

    A D Sorrell

  5. Peyton Manning Children's Hospital at St. Vincent, Indianapolis, IN, USA

    J M Hilden

  6. Division of Laboratory Genetics, Mayo Clinic, Rochester, MN, USA

    R P Ketterling

  7. Department of Oncology, Montefiore Medical Center, Bronx, NY, USA

    E Paietta

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  1. R Bhat
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  2. S Malinge
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Correspondence to J D Crispino.

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Bhat, R., Malinge, S., Gamis, A. et al. Mutational analysis of candidate tumor-associated genes in acute megakaryoblastic leukemia. Leukemia 23, 2159–2160 (2009). https://doi.org/10.1038/leu.2009.159

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