title: CBL mutation in chronic myelomonocytic leukemia secondary to familial platelet disorder with propensity to develop acute myeloid leukemia (FPD/AML).
abstract: Familial platelet disorder with a propensity to develop acute myeloid leukemia (FPD/AML) is a rare autosomal dominant disease characterized by thrombocytopenia, abnormal platelet function, and a propensity to develop myelodysplastic syndrome (MDS) and AML. So far, > 20 affected families have been reported. Recently, a second RUNX1 alteration has been reported; however, no additional molecular abnormalities have been found so far. We identified an acquired CBL mutation and 11q-acquired uniparental disomy (11q-aUPD) in a patient with chronic myelomonocytic leukemia (CMML) secondary to FPD with RUNX1 mutation but not in the same patient during refractory cytopenia. This finding suggests that alterations of the CBL gene and RUNX1 gene may cooperate in the pathogenesis of CMML in patients with FPD/AML. The presence of CBL mutations and 11q-aUPD was an important "second hit" that could be an indicator of leukemic transformation of MDS or AML in patients with FPD/AML.
authors.affiliation: Department of Hematology/Oncology, Gunma Children's Medical Center, Shibukawa, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Shiba
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hasegawa
authors.forename: Myoung-ja
authors.initials: MJ
authors.lastname: Park
authors.forename: Chisato
authors.initials: C
authors.lastname: Murata
authors.forename: Aiko
authors.initials: A
authors.lastname: Sato-Otsubo
authors.forename: Chitose
authors.initials: C
authors.lastname: Ogawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Manabe
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Arakawa
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D001791:Blood Platelet Disorders / Q000150:complications / Q000235:genetics*; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000235:genetics*; D015477:Leukemia, Myelomonocytic, Chronic / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human; D050721:Proto-Oncogene Proteins c-cbl; C067419:CBL protein, human