Ubiquitous expression of cytokines in diverse leukemias of lymphoid and myeloid lineage.
It has recently been suggested that autocrine production of hematopoietic regulatory molecules can modulate the cardinal features of many leukemic states: excessive proliferation of the neoplastic cells and suppression of the normal elements. We therefore analyzed samples obtained from 57 patients with a variety of hematologic malignancies (21, acute myelogenous leukemia; 14, acute lymphoblastic leukemia; 12, Philadelphia chromosome-positive chronic myelogenous leukemia [blast phase] or acute leukemia; 5, chronic lymphocytic leukemia; and 5, chronic myelomonocytic leukemia) for expression of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) transcripts on Northern blots. TNF-alpha mRNA was discerned in almost half of the samples (47%), and was expressed in some patients with every type of leukemia, except T-cell acute lymphoblastic leukemia (ALL). Expression occurred with great frequency in samples (12 of 15 [80%]) from monocytic (acute or chronic) leukemias, and from advanced chronic lymphocytic leukemia (4 of 5 samples [80%]). IL-1 beta transcripts were detected in 20 of 57 samples (35%). Its presence, like that of TNF-alpha, was ubiquitous, and only chronic lymphocytic leukemia and T-cell acute lymphoblastic leukemia cells consistently failed to produce IL-1 beta message. Therefore it appears that TNF-alpha and/or IL-1 beta mRNA can be found in the leukemic cells from a substantial subset of patients with B cell-derived acute lymphoblastic leukemia as well as with chronic and acute myeloid, monocytic or lymphocytic leukemias. Because these cytokines have potent direct and indirect effects on normal and malignant hematopoiesis, their widespread constitutive expression by neoplastic blood cells may play a fundamental role in driving the leukemic process.
Kurzrock
R
R
Department of Clinical Immunology and Biological Therapy, M.D. Anderson Cancer Center, Houston, Texas 77030.
Kantarjian
H
H
Wetzler
M
M
Estrov
Z
Z
Estey
E
E
Troutman-Worden
K
K
Gutterman
J U
JU
Talpaz
M
M
D015152:Blotting, Northern; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics; D007945:Leukemia, Lymphoid / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D007951:Leukemia, Myeloid / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha