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Mutations of polycomb‐associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia
Author(s) -
GelsiBoyer Véronique,
Trouplin Virginie,
Adélaïde José,
Bonansea Julien,
Cervera Nathalie,
Carbuccia Nadine,
Lagarde Arnaud,
Prebet Thomas,
Nezri Meyer,
Sainty Danielle,
Olschwang Sylviane,
Xerri Luc,
Chaffanet Max,
Mozziconacci MarieJoëlle,
Vey Norbert,
Birnbaum Daniel
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.07697.x
Subject(s) - myelodysplastic syndromes , haematopoiesis , myeloid , chronic myelomonocytic leukemia , biology , epigenetics , cancer research , gene , comparative genomic hybridization , mutation , genetics , genome , immunology , stem cell , bone marrow
Summary The myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal haematological diseases characterized by ineffective haematopoiesis and predisposition to acute myeloid leukaemia (AML). The pathophysiology of MDSs remains unclear. A definition of the molecular biology of MDSs may lead to a better classification, new prognosis indicators and new treatments. We studied a series of 40 MDS/AML samples by high‐density array‐comparative genome hybridization (aCGH). The genome of MDSs displayed a few alterations that can point to candidate genes, which potentially regulate histone modifications and WNT pathways (e.g. ASXL1 , ASXL2 , UTX , CXXC4 , CXXC5 , TET2 , TET3 ). To validate some of these candidates we studied the sequence of ASXL1 . We found mutations in the ASXL1 gene in four out of 35 MDS patients (11%). To extend these results we searched for mutations of ASXL1 in a series of chronic myelomonocytic leukaemias, a disease classified as MDS/Myeloproliferative disorder, and found mutations in 17 out of 39 patients (43%). These results show that ASXL1 might play the role of a tumour suppressor in myeloid malignancies.