Abstract
A clonal cytogenetic abnormality was observed in Philadelphia chromosome-negative bone marrow cells of 6/27 chronic myeloid leukemia patients (+8 in 4, -7 in 1, and 20q- in 1) with dasatinib-induced remissions. The X-linked human androgen receptor gene assay demonstrated clonality in one additional patient. Single nucleotide polymorphism array analysis revealed somatic uniparental disomy involving chromosome 17(p12-pter) in another patient. The TP53 gene had a 5' splice site deletion of exon 6 that caused alternative splicing, frame shifting and introduction of a premature stop codon. After three years, no patient developed myelodysplastic syndrome or acute myeloid leukemia.
Copyright 2009 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Antineoplastic Agents / therapeutic use
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Base Sequence
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Bone Marrow Cells / metabolism
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Bone Marrow Cells / pathology
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Bone Marrow Cells / physiology*
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Cell Differentiation / drug effects
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Cell Differentiation / genetics
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Clone Cells / drug effects
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Clone Cells / metabolism
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Clone Cells / pathology*
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Cytogenetic Analysis
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Dasatinib
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Female
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Follow-Up Studies
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Genes, p53
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Hematopoiesis / drug effects
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Hematopoiesis / genetics
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Hematopoiesis / physiology*
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Humans
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Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / drug therapy*
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Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / genetics
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Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / pathology
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Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / physiopathology*
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Male
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Middle Aged
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Molecular Sequence Data
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Philadelphia Chromosome
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Pyrimidines / therapeutic use*
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Thiazoles / therapeutic use*
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Treatment Outcome
Substances
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Antineoplastic Agents
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Pyrimidines
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Thiazoles
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Dasatinib