bcr-abl oncogene activation in Philadelphia chromosome-positive acute lymphoblastic leukemia.
Tumor-specific alterations in oncogenes are thought to play a central role in the development of cancer. An example is the consistent fusion of the bcr gene to the c-abl oncogene on the Ph chromosome in CML. The Ph chromosome can also be observed in ALL. About 50% of Ph+ ALL cases, in contrast to CML, do not exhibit chromosomal breakpoints in the major cluster region or mcr (Ph+ mcr- ALL). These cases may have a novel bcr-abl fusion gene instead. We tested this hypothesis in eight Ph+ mcr- ALL patients by amplifying the putative hybrid part of the bcr-abl cDNA, using the polymerase chain reaction method. All cases examined showed the same joining of the first exon of the bcr gene to the c-abl oncogene. Thus, the novel bcr-abl fusion in Ph+ mcr- ALL is the result of a molecularly distinct Ph chromosome. This allows the definition of Ph+ leukemias by their respective bcr-abl oncogene activation. Moreover, the cDNA amplification method we use is a clinically useful tool to screen for bcr-abl oncogene activations in leukemia patients.
Hermans
A
A
Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
Gow
J
J
Selleri
L
L
von Lindern
M
M
Hagemeijer
A
A
Wiedemann
L M
LM
Grosveld
G
G
D004273:DNA, Neoplasm / Q000235:genetics*; D006801:Humans; D021141:Nucleic Acid Amplification Techniques; D009857:Oncogenes; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011995:Recombination, Genetic
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm