P190BCR-ABL chronic myeloid leukaemia: the missing link with chronic myelomonocytic leukaemia?
Two-thirds of patients with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukaemia (ALL) have a breakpoint in the minor breakpoint cluster region (m-bcr) of the BCR gene, which results in an e1a2 transcript and a P190BCR-ABL fusion protein. This type of genomic rearrangement occurs very rarely in chronic myeloid leukaemia (CML); it has been reported in only four cases. We describe here a fifth case of P190 CML in which the cytomorphological characteristics were intermediate between CML and chronic myelomonocytic leukaemia (CMML). This case, and the four reported previously, had a consistent and significant monocytosis with a low neutrophil/monocyte ratio in the peripheral blood, resembling CMML. On the other hand, they also had a high percentage of circulating immature granulocytes, basophilia and low neutrophil alkaline phosphatase (NAP) score, which are more commonly found in classical CML. Thus, P190 CML may be a specific form of CML, in which the myeloproliferative process includes the monocytic, as well as the granulocytic lineage. Since the molecular defect in CML is thought to involve a pluripotent stem cell, the different effects of P210BCR-ABL and P190BCR-ABL in CML must reflect the somewhat wider spectrum of activity of the P190BCR-ABL. Other patients with atypical CML or CMML who lack a Ph chromosome may also have an m-bcr breakpoint which would not be detected on standard Southern blots, but which would be detectable by polymerase chain reaction amplification of reverse transcribed RNA.
Melo
J V
JV
Department of Haematology, Royal Postgraduate Medical School, London, UK.
Myint
H
H
Galton
D A
DA
Goldman
J M
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics* / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods
D004273:DNA, Neoplasm; D016044:Fusion Proteins, bcr-abl; D004262:DNA Restriction Enzymes