Cell-Cycle Characteristics - Alterable Determinants of Remission Duration in a Study of 179 Standard Risk Newly Diagnosed Patients With Acute Myeloid-Leukemia

Raza, Abbas; Yousuf, Naveed; Bokhari, S. A. J.; Abbas, Adeeb; Lampkin, BC; Pancoast, J.; Bismayer, John A.; Siegrist, Carl; Browman, G; Bennett, James; Goldberg, J. A.; Grunwald, H; Larson, Richard A.; Tricot, Guido; Vogler, Ralph; Gartside, Peter; Hd, Preisler

doi:10.3892/ijo.2.2.301

Cited by 4 publications

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“…Interestingly, in leukemia patients, TGF-b expression is often highly elevated (Raza et al, 1992;Mori et al, 2000). Given the fact that the TGF-b cytostatic effect in leukemogenesis may be impaired due to diverse mechanisms summarized in Figure 3, upregulation of TGF-b may instead promote leukemia progression and invasion.…”

Section: Discussionmentioning

confidence: 99%

Deregulated TGF-β signaling in leukemogenesis

2005

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Section: Discussionmentioning

confidence: 99%

Deregulated TGF-β signaling in leukemogenesis

2005

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Biological Significance of Proliferation, Apoptosis, Cytokines, and Monocyte/Macrophage Cells in Bone Marrow Biopsies of 145 Patients With Myelodysplastic Syndrome

et al. 2002

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Labeling index (LI), apoptosis, levels of 2 pro-apoptotic cytokines tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta(TGF-beta), and the number of monocyte/macrophage cells that are the likely source of the cytokines were simultaneously measured in plastic-embedded bone marrow (BM) biopsy sections of 145 patients with myelodysplastic syndromes (MDS). TNF-alpha was correlated with TGF-beta (P = .001) and with monocyte/macrophage cells (P = .003). Patients with excess blasts in their marrows had a higher TGF-beta level (P = .01) and monocyte/macrophage number (P = .05). In a linear regression model,TGF-beta emerged as the most significant biological difference between patients who have excess of blasts and those who do not (P = .01). We conclude that in addition to TNF-alpha, TGF-beta also plays a significant role in the initiation and pathogenesis of MDS, and that a more precise definition of its role will likely identify better preventive and therapeutic strategies.

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Thrombocytopenia in MDS: epidemiology, mechanisms, clinical consequences and novel therapeutic strategies

Morrone

Kambhampati

et al. 2015

Leukemia

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Thrombocytopenia is commonly seen in myelodysplastic syndrome (MDS) patients, and bleeding complications are a major cause of morbidity and mortality. Thrombocytopenia is an independent factor for decreased survival and has been incorporated in newer prognostic scoring systems. The mechanisms of thrombocytopenia are multifactorial and involve a differentiation block of megakaryocytic progenitor cells, leading to dysplastic, hypolobated and microscopic appearing megakaryocytes or increased apoptosis of megakaryocytes and their precursors. Dysregulated thrombopoietin (TPO) signaling and increased platelet destruction through immune or nonimmune mechanisms are frequently observed in MDS. The clinical management of patients with low platelet counts remains challenging and approved chemotherapeutic agents such as lenalidomide and azacytidine can also lead to a transient worsening of thrombocytopenia. Platelet transfusion is the only supportive treatment option currently available for clinically significant thrombocytopenia. The TPO receptor agonists romiplostim and eltrombopag have shown clinical activity in clinical trials in MDS. In addition to thrombopoietic effects, eltrombopag can inhibit leukemic cell proliferation via TPO receptor-independent effects. Other approaches such as treatment with cytokines, immunomodulating drugs and signal transduction inhibitors have shown limited activity in selected groups of MDS patients. Combination trials of approved agents with TPO agonists are ongoing and hold promise for this important clinical problem.

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Cell-Cycle Characteristics - Alterable Determinants of Remission Duration in a Study of 179 Standard Risk Newly Diagnosed Patients With Acute Myeloid-Leukemia

Cited by 4 publications

References 0 publications

Deregulated TGF-β signaling in leukemogenesis

Deregulated TGF-β signaling in leukemogenesis

Biological Significance of Proliferation, Apoptosis, Cytokines, and Monocyte/Macrophage Cells in Bone Marrow Biopsies of 145 Patients With Myelodysplastic Syndrome

Thrombocytopenia in MDS: epidemiology, mechanisms, clinical consequences and novel therapeutic strategies

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