Acute lymphoid leukemia molecular phenotype in a patient with benign-phase chronic myelogenous leukemia.
The benign phase of chronic myelogenous leukemia (CML) typically is characterized by an overproduction of myeloid cells that eventually progresses to a more acute stage termed blast crisis. This latter stage can exhibit either myeloid or lymphoid blast clones. Our recent results have demonstrated the presence of the P210 BCR-ABL protein in blood cells from benign phase CML patients (Guo et al., Cancer Research 51:3048, 1991). This protein is the product of an 8.5 kb chimeric RNA encoded by fused BCR-ABL genes produced by the formation of the Philadelphia (Ph) chromosome. Using this new assay we have identified a patient with benign-phase CML who produces P190 BCR-ABL, the form of the BCR-ABL protein found in about 50% of cases of acute lymphocytic leukemia (ALL). This patient lacked detectable P210 BCR-ABL protein and did not contain a DNA rearrangement in the major breakpoint cluster region of the BCR gene. Consistent with this result, polymerase chain reaction (PCR) analyses detected a BCR-ABL mRNA with BCR exon 1 fused to ABL exon 2. No BCR-ABL mRNAs with 2'- or 3'-bcr exon to ABL exon 2 fusions were detected in these analyses. Blood cells from this patient lost P190 BCR-ABL after the patient underwent an allogeneic bone marrow transplant, but regained this protein although the patient was still in chronic phase after a subsequent autologous transplant as treatment for graft failure. These findings indicate that P190 BCR-ABL alone is not sufficient to induce a blast crisis phenotype in leukemia patients who are Ph chromosome-positive.
Guo
J Q
JQ
Department of Molecular Pathology, University of Texas, M. D. Anderson Cancer Center, Houston 77030.
Hirsch-Ginsberg
C F
CF
Xian
Y M
YM
Stass
S A
SA
Champlin
R E
RE
Giralt
S A
SA
McCredie
K B
KB
Campbell
M L
ML
Arlinghaus
R B
RB
D001483:Base Sequence; D015139:Blotting, Southern; D015153:Blotting, Western; D002874:Chromosome Mapping; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D016044:Fusion Proteins, bcr-abl / Q000032:analysis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000150:complications* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D010677:Philadelphia Chromosome; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics
D015342:DNA Probes; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D016044:Fusion Proteins, bcr-abl