UBIQUITOUS EXPRESSION OF CYTOKINES IN DIVERSE LEUKEMIAS OF LYMPHOID AND MYELOID LINEAGE

It has recently been suggested that autocrine production of hematopoie tic regulatory molecules can modulate the cardinal features of many le ukemic states: excessive proliferation of the neoplastic cells and sup pression of the normal elements. We therefore analyzed samples obtaine d from 57 patients with a variety of hematologic malignancies (21, acu te myelogenous leukemia; 14, acute lymphoblastic leukemia; 12, Philade lphia chromosome-positive chronic myelogenous leukemia [blast phase] o r acute leukemia; 5, chronic lymphocytic leukemia; and 5, chronic myel omonocytic leukemia) for expression of interleukin-1beta (IL-1beta) an d tumor necrosis factor-alpha (TNF-alpha) transcripts on Northern blot s. TNF-alpha mRNA was discerned in almost half of the samples (47%), a nd was expressed in some patients with every type of leukemia, except T-cell acute lymphoblastic leukemia (ALL). Expression occurred with gr eat frequency in samples (12 of 15 [80%]) from monocytic (acute or chr onic) leukemias, and from advanced chronic lymphocytic leukemia (4 of 5 samples [80%]). IL-1beta transcripts were detected in 20 of 57 sampl es (35%). Its presence, like that of TNF-alpha, was ubiquitous, and on ly chronic lymphocytic leukemia and T-cell acute lymphoblastic leukemi a cells consistently failed to produce IL-1beta message. Therefore it appears that TNF-alpha and/or IL-1beta mRNA can be found in the leukem ic cells from a substantial subset of patients with B cell-derived acu te lymphoblastic leukemia as well as with chronic and acute myeloid, m onocytic or lymphocytic leukemias. Because these cytokines have potent direct and indirect effects on normal and malignant hematopoiesis, th eir widespread constitutive expression by neoplastic blood cells may p lay a fundamental role in driving the leukemic process.