In vitro culture of clonogenic leukaemic cells in acute myeloid leukaemia: growth pattern and drug sensitivity.
Bone marrow from 43 of 45 AML patients grew leukaemic colonies in culture with a technique using methyl-cellulose semi-solid medium and stimulation with PHA-leucocyte conditioned medium. Plating efficiency was significantly greater in M4FAB subtypes than in M1 or M2. The presence of Auer rods in cultured cells and the existence of cytogenetic abnormalities in both fresh and cultured blast cells in one patient confirmed the leukaemic origin of these colonies. These clonogenic cells were closely related to the growth fraction, as demonstrated by a high suicide index and a linear correlation between percentage of bone marrow blasts in S phase and plating efficiency. In vitro CFU-L sensitivity to cytosine-arabinoside (ARA-C) and to adriamycin (ADR) was tested in 22 patients treated with these two drugs. In the group sensitive in vitro to ARA-C (10 patients), 70% entered complete remission. In the resistant group (12 patients), only 25% had complete remission while 75% had resistant disease. Eight of 14 patients sensitive to ADR in vitro achieved complete remission, while five were resistant to chemotherapy. On the other hand, six of eight patients resistant in vitro were resistant in vivo. When drug sensitivities to ARA-C and ADR were cumulated, an excellent in vitro to in vivo correlation was found when the patient was sensitive or resistant to both drugs in vitro.
D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology*
D003561:Cytarabine; D004317:Doxorubicin