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Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3405-3409
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, and
H. Phillip Koeffler
From the Departments of Medicine and Clinical Pathology, Cedars-Sinai
Medical Center, UCLA School of Medicine, Los Angeles, CA; the
Hemostasis Research Center, Catholic University of Rome, Rome, Italy;
the Department of Hematology, Hadassah Medical Organization, Jerusalem,
Israel; the Department of Medicine, UCLA School of Medicine, Los
Angeles, CA; and the Department of Hematology, Tokyo Women's Medical
College, Tokyo, Japan.
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 D1S508 and distal to D1S507 (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.
© 1998 by The American Society of Hematology.
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