Induction of differentiation of myeloid leukemic cells by busulphan: in vivo and in vitro observations.
Treatment of a 74 year old patient with chronic myelogenous leukemia (CML) with busulphan resulted in an abrupt and pronounced decrease of the white blood cell (WBC) count with restoration of normal peripheral blood cell morphology and regression of splenomegaly. The Philadelphia positive (Ph+) clone was however still detectable. The alterations in the WBC count and morphology were not preceded by marrow hypoplasia but correlated closely with a marked decrease in the serum levels of Transcobalamin I (TC I), a vitamin B12-binding protein derived from immature myeloid precursors and a reciprocal rise in serum TC III, a vitamin B12-binding protein originating from terminally differentiated mature granulocytes. Studies on the HL-60 cell line showed that busulphan is capable of inducing leukemic cells to differentiate into granulocyte-like cells. These observations, taken together, suggest that in addition to its potent myelosuppressive effects, busulphan may induce apparent clinical remissions in some CML patients by promoting terminal cell differentiation.
Michaeli
J
J
Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
Fibach
E
E
Rachmilewitz
E A
EA
D000368:Aged; D001853:Bone Marrow / Q000187:drug effects; D002066:Busulfan / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D008297:Male; D014155:Transcobalamins / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D014155:Transcobalamins; D002066:Busulfan