Expression of thrombopoietin and its receptor (c-mpl) in chronic myelogenous leukemia

Kaban, Kerim; Kantarjian, Hagop M.; Talpaz, Moshe; O’Brien, Susan; Cortes, Jorge; Giles, Francis J.; Pierce, R N Sherry; Albitar, Mäher

doi:10.1002/(sici)1097-0142(20000201)88:3<570::aid-cncr12>3.0.co;2-i

Cited by 14 publications

(10 citation statements)

References 31 publications

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“…12 Therefore, there may be an association between aberrant c-sis expression, production of PDGF-like molecules, and excessive fibroblast stimulation and the development of myelofibrosis. Wetzler et al also have suggested that the bone marrow fibroblasts in CML may participate in disease progression through paracrine loops involving stimulating cytokines such as interleukin-6.…”

Section: Discussionmentioning

confidence: 99%

Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia

Bueso‐Ramos

Cortes

Talpaz

et al. 2004

Cancer

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BACKGROUNDReticulin‐stained bone marrow fibrosis is associated with a poor prognosis in patients with chronic myelogenous leukemia (CML). Resolution of fibrosis with therapy may improve patient outcome.METHODSThe effect of imatinib therapy on bone marrow fibrosis was evaluated in 40 patients with chronic‐phase CML who were treated after interferon‐α failure.RESULTSThirty‐one patients (78%) had severe (Grade 3 or 4) reticulin fibrosis prior to therapy. After imatinib therapy was administered for 3 to > 24 months, fibrosis was reduced by at least 2 grades in 19 of the 31 patients (61%) and by at least 1 grade in 34 patients (85%). There was no correlation noted between reduction of fibrosis and cytogenetic response. However, a reduction in fibrosis was found to correlate with a reduction in bone marrow megakaryocytosis (P = 0.002).CONCLUSIONSTreatment with imatinib mesylate appears to reduce CML‐associated bone marrow fibrosis in most patients who are treated during the chronic phase of disease. This effect may be independent of the degree of suppression of Philadelphia chromosome‐positive cells, and may improve prognosis in patients with CML. Cancer 2004. © 2004 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia

Bueso‐Ramos

Cortes

Talpaz

et al. 2004

Cancer

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“…The c-mpl protein was quantified by the solid-phase RIA method as previously described (17,18). The c-mpl protein was quantified by the solid-phase RIA method as previously described (17,18).…”

Section: Methodsmentioning

confidence: 99%

Platelet production and related pathophysiology in acute myelogenous leukemia at first diagnosis: Prognostic implications

Trafalis¹,

Poulakidas²,

Kapsimali³

et al. 2008

Oncol Rep

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Among various laboratory and clinical features megakaryocytopoiesis and platelet (PLT) counts have been previously insufficiently evaluated for their prognostic significance in acute myelogenous leukaemia (AML). We studied several clinical and laboratory features of 108 first diagnosed AML patients in relation with their prognosis. Patients with favourable prognostic features were excluded from the study. This study focused on the prognostic impact of PLT counts and related molecular biology in AML patients at initial diagnosis. In particular, the PLT counts were correlated with the endogenous production of thrombopoietin (TPO), c-mpl expression, CD34 + leukemic blast cell proportion, cytogenetics, and a prognostic correlation was established. We found that the most favorable prognosis appeared in the AML patient group with PLTs <25x10 9 /l and correlated to cytogenetic findings (normal or abnormal karyotypes), while by far the most unfavorable prognosis was found in the patient group with PLTs ≥130x10 9 /l independent of the corresponding cytogenetics. It was demonstrated that AML patients with normal or elevated PLT counts at first presentation, may constitute a distinct patient group with particular characteristics such as higher levels of endogenous TPO production, high expression of CD34 + leukemic blast cells, higher expression of c-mpl and consequently low response to chemotherapy and a very poor prognosis. These correlations between PLTs production (megakaryothrombo-poiesis), TPO serum levels and TPO receptor (c-mpl) expression may help in the determination of risk-adapted AML patient groups and of targeted therapeutic strategies.

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“…What causes marrow fibrosis in CML is unknown, but may be mediated by various cytokines such as the platelet-derived growth factor (PDGF), which is produced by megakaryocytes (clonal) and stimulates fibroblasts (non-clonal). Elevated levels of thrombopoietin and its receptor (C-MPL protein) were found in CML and correlated with thrombocytosis [22]. Other cytokines, such as interleukin-6, may also be involved [23].…”

Section: Resultsmentioning

confidence: 99%

“…This significant resolution of marrow fibrosis with imatinib therapy may further improve prognosis in CML through mechanisms either independent of or related to the suppression of Bcr-Abl [22,23]. It may also alter the prognostic relevance of the degree of marrow fibrosis in CML, the subject of this analysis.…”

Section: Introductionmentioning

confidence: 99%

The degree of bone marrow fibrosis in chronic myelogenous leukemia is not a prognostic factor with imatinib mesylate therapy

Kantarjian

Bueso‐Ramos

Talpaz

et al. 2005

Leukemia & Lymphoma

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One hundred and ten patients with Philadelphia chromosome (Ph)-positive chronic phase chronic myelogenous leukemia (CML) post-interferon-a failure treated with imatinib mesylate therapy were analyzed for the prognostic significance of marrow reticulin stain-measured fibrosis. The median time from diagnosis was 31 months. Severe reticulin (grade 3 - 4) fibrosis was observed in 67 patients (61%). Patients with severe marrow fibrosis had similar complete cytogenetic response rates with imatinib (67 vs. 58%; P = 0.45) compared with those with mild?-?moderate fibrosis. The estimated 4 year survival rates (80 vs. 88%; P = 0.27) and failure-free survival rates (69 vs. 77%; P = 0.34) were also not different. We conclude that the previously established poor prognostic significance of marrow fibrosis in CML is less relevant with imatinib therapy.

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Expression of thrombopoietin and its receptor (c-mpl) in chronic myelogenous leukemia

Cited by 14 publications

References 31 publications

Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia

Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia

Platelet production and related pathophysiology in acute myelogenous leukemia at first diagnosis: Prognostic implications

The degree of bone marrow fibrosis in chronic myelogenous leukemia is not a prognostic factor with imatinib mesylate therapy

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