Immunoglobulin and T cell receptor gene rearrangements in Philadelphia chromosome-positive leukemia: a different involvement pattern in blast crisis and acute leukemia.
We have analyzed the configuration of the immunoglobulin heavy (IgH) chain gene and the T cell receptor (TCR) chain (beta, gamma, and delta) genes in a group of 22 leukemia patients with the Philadelphia (Ph) chromosome. The group consisted of 14 patients with chronic myelogenous leukemia in blast crisis (CML-BC) and eight with Ph-positive acute leukemia (Ph + AL); these diagnoses were based on hematologic and cytogenetic features. In CML-BC patients, an IgH joining region rearrangement was detected only in patients with CD10 expression; TCR-beta, -gamma, or -delta rearrangements were associated with IgH involvement. In contrast, five of the eight Ph+ AL patients had breaks within the major breakpoint cluster region (M-BCR), and four of them had IgH involvement. Of the remaining three Ph+ M-BCR nonrearranged AL patients, only one showed IgH rearrangement. In addition, TCR-beta involvement was sometimes detected in Ph+ AL patients (two of the eight patients) with or without rearranged M-BCR, and no PH+ AL case displayed rearranged TCR-gamma. These findings suggest that genotypic changes in CML-BC are usually associated with phenotypic results of the neoplastic cells: the expression of CD10 in CML-BC patients is accompanied by the involvement of IgH with frequent TCR rearrangements which possibly are due to the common recombinase activity. On the other hand, the mechanism of the involvement of IgH in Ph+ AL patients without rearranged M-BCR seems different from that observed in Ph+ leukemia patients with rearranged M-BCR, although TCR involvement could occur whether or not the leukemia cells had a rearranged M-BCR in Ph+ AL patients.
Ohyashiki
J H
JH
First Department of Internal Medicine, Tokyo Medical College, Japan.
Ohyashiki
K
K
Tauchi
T
T
Saito
M
M
Nakazawa
S
S
Kimura
N
N
Toyama
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D001752:Blast Crisis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002648:Child; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D005838:Genotype; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015260:Neprilysin; D009857:Oncogenes; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D015260:Neprilysin