P190(BCR-ABL) CHRONIC MYELOID-LEUKEMIA - THE MISSING LINK WITH CHRONIC MYELOMONOCYTIC LEUKEMIA

Two-thirds of patients with Philadelphia (Ph) chromosome-positive acut e lymphoblastic leukaemia (ALL) have a breakpoint in the minor breakpo int cluster region (m-bcr) of the BCR gene, which results in an e1a2 t ranscript and a P-190(BCR-ABL) fusion protein. This type of genomic re arrangement 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 intermed iate between CML and chronic myelomonocytic leukaemia (CMML). This cas e, and the four reported previously, had a consistent and significant monocytosis with a low neutrophil/monocyte ratio in the peripheral blo od, resembling CMML. On the other hand, they also had a high percentag e of circulating immature granulocytes, basophilia and low neutrophil alkaline phosphatase (NAP) score, which are more commonly found in cla ssical CML. Thus, P190 CML may be a specific form of CML, in which the myeloproliferative process includes the monocytic, as well as the gra nulocytic lineage. Since the molecular defect in CML is thought to inv olve a pluripotent stem cell, the different effects of P210(BCR-ABL) a nd P190(BCR-ABL) in CML must reflect the somewhat wider spectrum of ac tivity of the P190(BCR-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 detect able by polymerase chain reaction amplification of reverse transcribed RNA.