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    The Wiskott-Aldrich-Syndrome family member 1 (WASF1) gene on 6q21 is down-regulated in specific AML cytogenetic subtypes.
    Blood (2003)
    Silvana DebernardiFrederik W. van DelftAndrew G. DaviesDebra M. LillingtonM. A. Ferguson SmithTA ListerVaskar SahaB D YoungJ. Fitzgibbon
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    Keywords:
    Wiskott–Aldrich syndrome
    Topics:
    Cellular Mechanics and Interactions
    Cell Adhesion Molecules Research
    Mutations of the AML1 gene in acute myeloid leukemia of FAB types M0 and M7
    Genes Chromosomes and Cancer (2002)
    Stephen E. LangabeerRosemary E. GaleSara RollinsonGareth J. MorganDavid C. Linch
    Abstract The AML1 gene encodes a transcription factor that, together with its heterodimeric partner CBFB, regulates a number of target genes that are essential for normal hemopoiesis. In acute myeloid leukemia (AML), AML1 is disrupted not only by chromosomal translocations but also by mutations in the runt domain, which binds both DNA and CBFB. Acquired mutations have been described predominantly in the AML FAB type M0. To date, most patients appear to have biallelic disease, suggesting a complete lack of normal AML1 function. Inherited loss of function mutations thought to lead to haploinsufficiency also have been described in patients who have a familial disorder with predisposition to AML (FPD/AML), indicating the role of AML1 in megakaryopoiesis. Using single‐strand conformation polymorphism analysis, we studied the AML1 runt domain in 41 patients with M0 AML and identified potentially pathologic mutations in five (12%). Biallelic disease could be confirmed in only one patient, using loss of heterozygosity studies. At least three of the mutations would lead to truncated proteins similar to those reported in FPD/AML, suggesting that haploinsufficiency plays a role in the pathogenesis of this minimally differentiated type of leukemia. The incidence of acquired mutations in AML patients with acute megakaryoblastic leukemia (FAB type M7) was the same as that reported in other non‐M0 patients, with only one mutation detected in 20 (5%) patients studied. © 2002 Wiley‐Liss, Inc.
    Haploinsufficiency
    RUNX1
    Pathogenesis
    Loss function
    Acute megakaryoblastic leukemia
    Citations (60)
    Bi‐allelic deletions within 13q14 and transient trisomy 21 with absence of GATA1s in pediatric acute megakaryoblastic leukemia
    Pediatric Blood & Cancer (2011)
    Stephanie MassaroRenu BajajFarzana PashankarDeborah L. OrnsteinPatrick G. Gallagher
    Oligonucleotide array comparative genomic hybridization, karyotype and fluorescence in situ hybridization analyses were employed to delineate the cytogenetic abnormalities in a case of pediatric acute megakaryoblastic leukemia. Here we present a unique genetic profile that includes bi-allelic deletions within 13q14, where the retinoblastoma tumor suppressor gene (RB1) resides, as well as isolated trisomy 21 without a concomitant mutation in the hematopoietic transcription factor GATA1s and translocation (17;22), that does not involve the megakaryoblastic leukemia 1 (MKL1) gene located on chromosome 22. Alteration of the RB1 gene is most likely the critical leukemogenic event in this patient.
    Acute megakaryoblastic leukemia
    Trisomy
    Comparative genomic hybridization
    Citations (5)
    Identification of new classes among acute myelogenous leukaemias with normal karyotype using gene expression profiling
    Oncogene (2004)
    Norbert VeyJulien MozziconacciAgnès Groulet-MartinecStéphane DebonoPascal Finetti
    Identification
    Citations (47)
    Cooperation of activating Ras/rtk signal transduction pathway mutations and inactivating myeloid differentiation gene mutations in M0 AML: a study of 45 patients
    Leukemia (2006)
    Christophe RoumierS. Lejeune-DumoulinAline RennevilleA S GoethgeluckN Philippe
    PTPN11
    Citations (18)
    Hyperactivation of the RAS signaling pathway in myelodysplastic syndrome with AML1/RUNX1 point mutations
    Leukemia (2006)
    Hiromasa NiimiHironori HaradaYuka HaradaYahui DingJun Imagawa
    RUNX1
    PTPN11
    Citations (68)
    Mutations of genes in the receptor tyrosine kinase (RTK)/RAS-BRAF signal transduction pathway in therapy-related myelodysplasia and acute myeloid leukemia
    Leukemia (2005)
    Debes H. ChristiansenMette Klarskov AndersenF DestaJ Pedersen-Bjergaard
    CEBPA
    PTPN11
    Citations (125)
    Defects in the RAS/RTK Signaling Pathways Predominate the Mutational Spectrum of EVI1/GATA2 Rearranged Myeloid Malignancies with Inv(3)/t(3;3)
    Blood (2014)
    Mathijs A. SandersStefan GröschelRemco M. HoogenboezemAnnelieke ZeilemakerMarije Havermans
    GATA2
    Citations (0)
    Point mutations in the RUNX1/AML1 gene: another actor in RUNX leukemia
    Oncogene (2004)
    Motomi Osato
    RUNX1
    Haploinsufficiency
    Platelet disorder
    Citations (271)
    Molecular pathology of leukemia
    Cambridge University Press eBooks (2010)
    Maher AlbitarAmber C. Donahue
    Most of the current knowledge of the molecular basis of leukemias indicates that leukemias are heterogeneous groups of neoplasms. Even when the clinical and phenotypic presentations are similar, biologically the leukemias may differ, and molecular characterization of the individual leukemia is therefore essential for predicting prognosis and determining therapeutic approaches. This observation is not only relevant to leukemias, but is true of the complexity of cancer in general.
    Citations (1)
    RAS mutations in pediatric leukemias withMLL gene rearrangements
    Genes Chromosomes and Cancer (1998)
    Nidal MahgoubRobert I. ParkerMatthew R. HoslerPamelyn CloseNaomi J. Winick
    Translocations of the MLL gene at chromosome band 11q23 are the most common cytogenetic alterations in de novo leukemia in infants and in leukemia related to chemotherapy with DNA topoisomerase II inhibitors. Experiments on knock-in mice suggest that additional mutational events may by required for full leukemogenesis. Therefore, we used single-strand conformation polymorphism analysis and an allele-specific restriction enzyme assay to investigate the frequency of KRAS and NRAS mutations in 32 pediatric leukemias with translocation of the MLL gene. Of 25 de novo cases, 13 were acute lymphoblastic leukemia (ALL), 10 were acute myeloid leukemia (AML), and 2 were biphenotypic. Three secondary leukemias were AML, 1 was biphenotypic, 1 was ALL, and 2 were diagnosed as myelodysplasia. The frequency of RAS mutations was 2 of 10 in de novo AML. Both mutations occurred in infant monoblastic variants. RAS mutations were otherwise absent in this series. This is the first report of congenital leukemias where translocation of the MLL gene and RAS mutation coexist. The frequency of RAS mutations in de novo AMLs with MLL gene translocations is similar to that in other forms of AML, but RAS mutations play a limited role in lymphoid and treatment-related leukemias with similar translocations.
    Citations (40)