Loss of heterozygosity on chromosome 5 in adults with acute lymphoblastic leukemia.
Cytogenetic abnormalities are among the most important pretreatment predictors of outcome in patients with acute lymphoblastic leukemia (ALL). Deletions of genetic material can result in loss of tumor suppressor genes or other translation products that are crucial in maintaining an orderly cell cycle sequence or viability of the apoptotic cascade. Chromosome 5 contains many genes that are relevant in hematopoiesis. Deletions of chromosome 5 or parts thereof are found frequently in myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML) where they are associated with a poor prognosis. Although abnormalities of chromosome 5 are not commonly detected by cytogenetic analysis in patients with acute lymphoblastic leukemias, we hypothesized that loss of heterozygosity (LOH) of microsatellite markers on chromosome 5 may occur more frequently and likewise influence outcome in these patients. Therefore, we analyzed peripheral blood and bone marrow samples of 41 adults with a diagnosis of ALL for LOH by polymerase chain reaction (PCR) and correlated our findings with overall survival of patients with and without LOH. LOH for at least one microsatellite marker was found in seven of 41 patients (17%). All patients demonstrated LOH on the long arm of chromosome 5. In three patients, LOH was extended to 5p. A region of minimal deletion which overlapped in all seven patients could be localized between markers D5S410 and D5S436 corresponding to chromosomal location 5q31-33 which is similar to the area of minimal deletion seen in AML. None of these patients showed involvement of chromosome 5 by cytogenetic analysis. We conclude that patients with ALL have LOH for gene segments on chromosome 5, especially 5q, more frequently than expected from cytogenetic studies. Although, unlike AML, no significant impact on prognosis could be found between patients with and without LOH on chromosome 5. The current data suggest that 5q abnormalities are not specific for AML and can also occur in patients with ALL.
Faderl
S
S
Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4095, USA.
Gidel
C
C
Kantarjian
H M
HM
Manshouri
T
T
Keating
M
M
Albitar
M
M
D000328:Adult; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D016019:Survival Analysis