IDENTIFICATION OF GROWTH FACTOR-RESPONSIVE ACUTE MYELOGENOUS LEUKEMIABASED 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 marr ow samples were grown in suspension. Samples were classified as GF-dep endent (61%), or GF-independent (39%) based on maintenance of Ki67+ ce ll number (proliferating cells) in the absence of exogenous GFs. GF-de pendent samples had significant proliferative responses to steel facto r (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 fo r GF-independent cases; several were inhibited by exogenous GFs. SF wa s additive or synergistic with GM-CSF or IL-3 among GF-dependent cases ; however, combinations were no more effective than single cytokines a mong 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 individu al cytokines for any population. Flow cytometric determination of GF r eceptor expression was less predictive of GF response than was surviva l and proliferation in the absence of GFs. Suspension cultures in the absence of GFs can select patients most likely to benefit from therape utic strategies using GFs for cell cycle recruitment.