Clonal hematopoiesis in Philadelphia chromosome-negative bone marrow cells of chronic myeloid leukemia patients receiving dasatinib.
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.
Paquette
Ronald L
RL
Department of Medicine, UCLA, 42-121 CHS, Los Angeles, CA, USA. paquette@ucla.edu
Nicoll
John
J
Chalukya
Meenal
M
Gondek
Lucas
L
Jasek
Monika
M
Sawyers
Charles L
CL
Shah
Neil P
NP
Maciejewski
Jaroslaw
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020732:Cytogenetic Analysis; D000069439:Dasatinib; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010677:Philadelphia Chromosome; D011743:Pyrimidines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib