transforming-growth-factor-alpha and Leukemia--Myeloid--Acute

Transforming growth factor α (TGFα) is a peptide growth factor known to be expressed in normal haemopoiesis. It is also expressed in a range of epithelial neoplasms but has not been assessed in haemopoietic malignancies. We have performed an immunohistochemical evaluation of TGFα in acute and chronic myeloid malignancies.. TGFα expression was semiquantitatively assessed in 69 normal bone marrow trephines and 157 cases of myeloid malignancy using an immunohistochemical approach.. Blast cells of myeloid origin in acute myeloid leukaemia (AML), myelodysplasia and accelerated and blast phases of chronic myeloid leukaemia (CML) were TGFα positive. In acute promyelocytic leukaemia the neoplastic cells had significantly weaker TGFα expression than seen in other forms of AML. The blast cells in CML-accelerated and blast phases were positive with similar expression to AML.. TGFα is expressed in neoplastic myeloblasts and could, therefore, be used as blast cell biomarker in diagnostic haematopathology. In addition, TGFα immunohistochemistry may be of use in identifying a therapeutic target.

Topics: Biomarkers; Bone Marrow; Hematopoiesis; Humans; Immunohistochemistry; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Leukocytes; Myelodysplastic Syndromes; Myeloproliferative Disorders; Transforming Growth Factor alpha

ML-1 human myeloblastic leukemia cells, suspended in RPMI-1640 medium, differentiated to monocyte or macrophage-like cells when either tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), or tetradecanoylphorbol acetate (TPA) was added prior to or simultaneously with fetal bovine serum (FBS). When FBS was applied first, and followed, after washing, by the cytokines or by TPA, maturation did not occur. A 77 kDa glycoprotein (DF77), isolated from human leukocyte-conditioned medium and present in FBS, was capable of replacing FBS for induction of differentiation. Thus, in this cell system, TNF-alpha, TGF-beta, and TPA acted as competence factors, whereas DF77 acted as the progression signal. Optimal competence was established after exposure of the cells to TPA or to either of the cytokines for approximately 2 or 30 min, respectively. After removal of the factors, competence was retained for approximately 3 hr before it declined. These results demonstrate that the initiation of ML-1 human myeloblastic leukemia cell differentiation relied upon the sequential and ordered input of competence and progression signals.

Topics: Cell Differentiation; Humans; Leukemia, Myeloid, Acute; Tetradecanoylphorbol Acetate; Time Factors; Transforming Growth Factor alpha; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha