MYELOID NEOPLASIA Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells
نویسندگان
چکیده
1Division of Pathology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; 2Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; 3State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China; 4The Ohio State University Comprehensive Cancer Center, Columbus, OH; 5Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; 6Harvard Stem Cell Institute, Harvard Medical School, Boston, MA; 7Cancer Science Institute, National University of Singapore, Singapore; and 8Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
منابع مشابه
Mll partial tandem duplication induces aberrant Hox expression in vivo via specific epigenetic alterations.
We previously identified a rearrangement of mixed-lineage leukemia (MLL) gene (also known as ALL-1, HRX, and HTRX1), consisting of an in-frame partial tandem duplication (PTD) of exons 5 through 11 in the absence of a partner gene, occurring in approximately 4%-7% of patients with acute myeloid leukemia (AML) and normal cytogenetics, and associated with a poor prognosis. The mechanism by which ...
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RUNX1/CBFβ (core binding factor [CBF]) is a heterodimeric transcription factor complex that is frequently involved in chromosomal translocations, point mutations, or deletions in acute leukemia. The mixed lineage leukemia (MLL) gene is also frequently involved in chromosomal translocations or partial tandem duplication in acute leukemia. The MLL protein interacts with RUNX1 and prevents RUNX1 f...
متن کاملThe Mll partial tandem duplication: differential, tissue-specific activity in the presence or absence of the wild-type allele.
The partial tandem duplication of MLL (MLL-PTD) is found in 5% to 10% of patients with acute myeloid leukemia (AML) and normal cytogenetics. Its expression in leukemic blasts is coincident with a silenced wild-type (WT) MLL allele. We therefore generated mice expressing the Mll-PTD in the absence of Mll-WT. These Mll(PTD/-) mice die at birth unlike the normal life expectancy of Mll(PTD/WT), Mll...
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Acute myeloid leukemia (AML) as a distortion of blood cells involves the differentiation of hematopoietic stem cells. Several studies established the irregular overexpression of specific genes is a common finding in patients with AML. The ectopic viral integration site-1 (EVI1) gene is a proto-oncogene subject to alternative splicing, and encodes a zinc-finger protein that acts as a tr...
متن کاملLong-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: a Cancer and Leukemia Group B study.
The clinical impact of MLL partial tandem duplication (MLL-PTD) was evaluated in 238 adults aged 18 to 59 years with cytogenetically normal (CN) de novo acute myeloid leukemia (AML) who were treated intensively on similar Cancer and Leukemia Group B protocols 9621 and 19808. Twenty-four (10.1%) patients harbored an MLL-PTD. Of those, 92% achieved complete remission (CR) compared with 83% of pat...
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