Evidence for two molecular steps in the pathogenesis of myeloid disorders associated with deletion of chromosome 7 long arm

Abstract

Partial deletion of the long arm of chromosome 7 (7q−) is a frequent chromosomal aberration in many neoplasias, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Recurrent deletions, leading to loss of heterozygosity (LOH), may be indicative of a tumor suppressor gene nearby. We studied eight AML or MDS patients with 7q−, in order to define the commonly deleted area in more detail. Separated blood lymphocytes and granulocytes were typed with 48 polymorphic microsatellite markers, and the heterozygosity between the two cell lineages was compared. The minimum commonly deleted region spanned from D7S658 to D7S655. Unexpectedly, four of the patients showed remarkable homozygosity in both lymphocytes and granulocytes around the commonly deleted area, and thus no deletions could be demonstrated by comparing the two cell lineages. Comparison to leukemic patients without 7q− and to normal individuals revealed that the homozygosity was restricted to patients with 7q−. We suggest that a specific mechanism, such as mitotic recombination in bone marrow stem cells, leading to homozygosity in both granulocytes and lymphocytes, represents a leukemogenetic step in these patients.