Expression and prognostic value of hemopoietic cytokine receptors in acute myeloid leukemia (AML): implications for future therapeutical strategies

: Objectives: Hemopoietic cytokines regulate hemopoietic cell functions via specific cell surface receptors. There is evidence to suggest, that those receptors (R) could play a role in leukemia with respect to cell differentiations and its regulation, prognosis, and pathobiology. Knowledge of individual cytokine receptor (CKR) profiles could provide new discoveries about CKR‐supported therapeutic considerations. Methods: We have studied the expression of CKR on mononuclear bone marrow (BM) cells of 89 patients with acute myeloid leukemia (AML) at first diagnosis, three patients at relapse or with persisting AML and eight healthy probands by fluorescence‐activated cell sorting (FACS) analysis using directly fluorescein‐conjugated antibodies: CD114 (hG‐CSF‐R), CD116 (hGM‐CSF‐R), CD117 (hSCF‐R), CD123 (hIL‐3‐R), CD130 (gp130subunit), CD135 (hFL‐R). A case was defined as positive, if more than 20% of the cells expressed the regarding CKR. Results: All investigated CKR were more frequently expressed in AML‐samples than in healthy BM‐samples, except CD130, which was only expressed on 5–6% of AML‐blasts in all and with only one healthy BM‐sample being CD130+. Within the French–American–British (FAB) types we observed a maturation‐ and lineage (granulocytic/monocytic)‐committed expression profile. Monocytic subtypes (FAB‐type M4/M5) showed significantly more GM‐CSF‐R+ (P = 0.001) and FL‐R+ (P = 0.001) and significantly less stem cell factor‐R (SCF‐R+) (P = 0.02) cases. Highest proportions of G‐CSF‐R+ blasts were observed in FAB‐type M3. In undifferentiated leukemias (FAB‐type M1, M2) high amounts of SCF‐R+, IL‐3‐R+, and FL‐R+ blasts could be detected. FL‐R was the only CKR, which was positive in FAB‐type M0 (n = 2). No differences in CKR‐expression were detected between primary (p) and secondary (s). Separating our patient cohorts in cytogenetic risk groups we could detect a significant higher proportion of G‐CSF‐R+ blasts in the cytogenetic good risk group than in the bad risk group (P = 0.027), but G‐CSF‐R‐expression did not correlate with remission‐rate or relapse‐free survival probability of the patients. For clinical evaluation only patients treated by the AML‐CG‐protocol, were included (n = 53). There were no differences of CKR‐expression in the responder and non‐responder group, however, significant lower relapse‐free survival probabilities for patients with more than 85.5% FL‐R+ (P = 0.001) and more than 45.5% SCF‐R+ blasts were found (P = 0.02). Patien