Chromosome band 1p36 contains a putative tumor suppressor gene important in the evolution of chronic myelocytic leukemia

Naoki Mori*, Roberta Morosetti, Susanne Spira, Stephen Lee, Dina Ben-Yehuda, Gary Schiller, Raffaele Landolfi, Hideaki Mizoguchi, H. Phillip Koeffler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Chronic myelocytic leukemia (CML) is a common neoplasm of hematopoietic pluripotent stem cells. Although the evolution from chronic phase to blast crisis (BC) in CML patients is an inevitable clinical feature, little is understood about the mechanisms responsible for the transformation. We have previously performed allelotype analysis in CML BC and have detected frequent loss of heterozygosity (LOH) on the short arm of chromosome 1. To know the common region of LOH where a putative tumor suppressor gene may reside, deletional mapping was performed using 33 microsatellite markers spanning chromosome 1 in 30 patients with CML BC (21 myeloid and 9 lymphoid). DNA was extracted from slides of bone marrow smears or from bone marrow mononuclear cells. In each patient, DNA from chronic phase was analyzed alongside DNA from either their BC or accelerated phase. Allelic loss on 1p was observed in 14 of the 30 individuals (47%): 10 of the 21 myeloid and 4 of the 9 lymphoid BC cases. Serial cytogenetic information was available in 10 cases with LOH on 1p; interestingly, deletions in this region were not detected. Two samples showed LOH at all informative loci on 1p, whereas the other 12 samples showed LOH on at least one but not all loci on 1p. The common region of LOH resided proximal to DLS508 and distal to DLS507 (1p36). Our results suggest that a tumor suppressor gene that frequently plays an important role in the evolution to BC resides on 1p36 in CML.

Original languageAmerican English
Pages (from-to)3405-3409
Number of pages5
JournalBlood
Volume92
Issue number9
DOIs
StatePublished - 1 Nov 1998

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