The relationship between the type of bcr-abl hybrid messenger RNA and thrombopoiesis in Philadelphia-positive chronic myelogenous leukemia.
Formation of the Philadelphia (Ph1) chromosome, which contains the hybrid bcr-abl gene, is thought to be the initial event in chronic myelogenous leukemia (CML). The positions of the breakpoint within the breakpoint cluster region (bcr) on the bcr-abl gene in 22 chronic-phase cases of Ph1-positive CML were determined using conventional Southern blots, and the splicing pattern were also determined the species of the fused bcr-abl mRNA in 79 CML cases using the polymerase chain-reaction procedure (RT-PCR). The location of the breakpoint within the bcr locus was assigned to one of five zones. Breakpoints in zones 1 and 2 were grouped as 5', and those in zones 3, 4 and 5 as 3'. Nine patients had 5' breakpoints and 13 patients had 3' breakpoints. The platelet counts of 3' patients were significantly higher than those of 5' patients (1395 vs 274 x 10(9)/L; p < 0.03). The megakaryocyte counts from bone marrow histological sections in 3' patients (n = 12) and 5' patients (n = 7) were 63.4/mm2 and 19.5/mm2, with a significant difference at p < 0.006. The mean number of megakaryocyte progenitor cells assayed by in vitro cloning was 128.3/2 x 10(5) bone marrow cells for 3' patients (n = 7) compared with 46.3 for 5' patients (n = 4). Using the RT-PCR technique, the bcr exon 2/abl exon 2 fused mRNA (b2-a2) was detected in 18 patients, the bcr exon 3/abl exon 2 fused mRNA (b3-a2) was detected in 45 patients, and both types of mRNA were detected in 16 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
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Inokuchi
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Nomura
D001483:Base Sequence; D001792:Blood Platelets / Q000502:physiology*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D016313:Genes, abl; D006410:Hematopoiesis; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics*; D008533:Megakaryocytes; D008969:Molecular Sequence Data; D010976:Platelet Count; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016044:Fusion Proteins, bcr-abl