Identification of growth factor-responsive acute myelogenous leukemia based on factor-dependence for survival and proliferation.
To determine whether a requirement for exogenous growth factors (GFs) for survival and proliferation could identify cases of AML which would respond best to GFs, singly and in combination, primary AML bone marrow samples were grown in suspension. Samples were classified as GF-dependent (61%), or GF-independent (39%) based on maintenance of Ki67+ cell number (proliferating cells) in the absence of exogenous GFs. GF-dependent samples had significant proliferative responses to steel factor (SF), GM-CSF and IL-3; mean Ki67+ cell number increased by 4.1-, 3.3-, and 5.2-fold, respectively. Significant stimulation was not seen for GF-independent cases; several were inhibited by exogenous GFs. SF was additive or synergistic with GM-CSF or IL-3 among GF-dependent cases; however, combinations were no more effective than single cytokines among the GF-independent group. GM-CSF plus IL-3 or the hybrid protein PIXY 321 did not increase the mean Ki67 ratio compared to the individual cytokines for any population. Flow cytometric determination of GF receptor expression was less predictive of GF response than was survival and proliferation in the absence of GFs. Suspension cultures in the absence of GFs can select patients most likely to benefit from therapeutic strategies using GFs for cell cycle recruitment.
Johns Hopkins Oncology Center, Baltimore, MD 21287-8963.
S D
SD
Gore
L J
LJ
Weng
P J
PJ
Burke
D000328:Adult; D000368:Aged; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D019394:Ki-67 Antigen; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D017978:Receptors, Growth Factor