Analysis of thrombopoietin receptor (c-mpl) mRNA expression in de novo acute myeloid leukemia

Schröder, J; Kolkenbrock, Sara; Tins, Jutta; Kasimir‐Bauer, Sabine; Seeber, S.; Schütte, J.

doi:10.1016/s0145-2126(99)00201-5

Cited by 12 publications

(11 citation statements)

References 39 publications

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“…In our cases c-MPL expression was found in 63.4% of AML and was associated with females and low leukocyte counts and over expression of c-MPL to M2 FAB subtype and AML with low percentage of blast in BM and in PB. Our study failed to confirm the correlation between expression of c-MPL and the cytogenetic prognostic groups described by Albitar [38], perhaps because of the limited number of cases with recurrent chromosomal translocations included in the study, but showed an association of c-MPL expression and expression of CD34 antigen as described by Schroder JK [36]. We found expression of c-Mpl in leukemic cells with intermediate differentiation, most of them FAB M2 with CD34 antigen.…”

Section: Discussioncontrasting

confidence: 72%

“…In normal hematopoiesis and also in human acute myeloid leukemia expression of c-Mpl seems to be regulated by Gata-1 [33]. Expression of c-MPL has been described in 50 to 65% of primary AML (MO, M2, M4, and M7 FAB subtypes) and in most cases of refractory anemia with excess blast (RAEB) and chronic myelomonocytic leukemia [34][35][36][37] although a recent study of 237 AML patients by the Medical Research Council (MRC) United Kingdom, using conventional RT-PCR, found c-Mpl expression in only one third of the patients and failed to show correlation with age, sex, or FAB subtype [34]. In our cases c-MPL expression was found in 63.4% of AML and was associated with females and low leukocyte counts and over expression of c-MPL to M2 FAB subtype and AML with low percentage of blast in BM and in PB.…”

Section: Discussionmentioning

confidence: 99%

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Clinical significance of Gata‐1, Gata‐2, EKLF, and c‐MPL expression in acute myeloid leukemia

et al. 2008

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The aim of this study was to evaluate the biological correlation and prognostic impact of Gata-1, Gata-2, EKLF, and c-MPL transcript level in a group of 41 acute mieloid leukemia (AML) patients. Gata-1 overexpression was related to advanced age and a low percentage of bone marrow blasts and was associated with the expression of CD34 antigen and lymphoid T markers. The negative impact of Gata-1 expression on the probability of achieving complete remission has been confirmed. Gata-2 overexpression was associated with a low percentage of blasts in BM and males. Expression of c-MPL was associated with CD341 AML and M2 FAB AML subtype. A higher expression of EKLF was found in secondary AML versus primary AML. Nevertheless, patients expressing EKLF had a longer overall survival and event free survival than those patients that did not express EKLF. Our study has identified expression of EKLF as a factor with a favorable impact on prognosis in AML. Am. J. Hematol. 84:79-86, 2009. V V C 2008 Wiley-Liss, Inc. IntroductionBlood cells are derived from a small number of pluripotent hematopoietic stem cells (HSCs) endowed with the capacity for self-renewal [1]. Specific hematopoietic transcription factors are crucial for self renewal, choice of cell fate, and cell differentiation during normal hematopoiesis [2]. Acute myeloid leukemia (AML) is characterized by the uncontrolled proliferation of myeloid cells that accumulate at various stages of development, where their further differentiation appears to be blocked. Although disturbance of the expression of transcription factors regulating proliferation, survival, and differentiation of myeloid progenitors is almost certainly a requisite for the pathogenesis of AML, a direct link to myeloid leukemogenesis has been formally demonstrated in only a few transcription factors [2].In AML, disruptions of transcription factors themselves seem to be able to enhance and/or block proliferation of the leukemic cells [2-4] because of either the effect on the factors of fusion proteins generated by chromosomal translocations or mutations in the transcription factors.However, even in the absence of the alterations previously mentioned, deregulation of hematopoietic transcription factors is to be expected in AML cells. Recent studies have provided evidence that differential expression of a limited number of genes, that include certain transcription factors, can be useful to classify AML and are related to variations in patient survival [5][6][7][8].Relevant changes in megakaryocytic and erythroide linage are a feature of M6 and M7 AML, but changes in transcription factors involved in erythroid and megakaryocyte differentiation can also be expected in other AML subtypes. The expression of the transcription factors involved in differentiation of the common bipotent progenitor [9] could affect the clinical course and response to treatment of all types of AML.With the purpose of bringing forward information in the deregulation of normal hematopoetic factors in AML, expression of several transcript...

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Section: Discussioncontrasting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Clinical significance of Gata‐1, Gata‐2, EKLF, and c‐MPL expression in acute myeloid leukemia

et al. 2008

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“…Patients with high c-mpl expression appeared to belong to a subgroup of AML with a low rate of complete remission and a poor prognosis, including secondary leukemia and AML with unfavourable cytogenetic abnormalities (10,16,17,26). We have studied the expression of c-mpl in a series of 105 patients with hematologic malignancies using Northern blot analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Data were analyzed and CD34 expression >10% of the blast population was interpreted as significant expression (16). The determination of CD34 expression on mononuclear cells that were collected with Ficoll-separation from the peripheral blood of the studied pts was performed with flow cytometry methods.…”

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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“…Regarding the correlation of c-MPL expression with AML patient characteristics and survival, Ebrahim et al's study showed that negative expression of CD34 and c-MPL may predict longer OS [36]. By evaluating the correlation of c-MPL expression with treatment response, Schroder et al found that a higher complete remission rate was achieved in c-MPLnegative patients than in c-MPL-positive patients [37]. Taken together with the results of Wetzler et al's study [38], their results suggest that c-MPL represents an adverse prognostic factor for treatment outcome in adult AML.…”

Section: Discussionmentioning

confidence: 99%

c-MPL Is a Candidate Surface Marker and Confers Self-Renewal, Quiescence, Chemotherapy Resistance, and Leukemia Initiation Potential in Leukemia Stem Cells

Zhao

et al. 2018

Stem Cells

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Acute myeloid leukemia (AML) is initiated and maintained by a unique, small subset of leukemia cells known as leukemia stem cells (LSCs). Self-renewal, quiescence, and chemotherapy resistance are key stemness properties of LSCs that are essential for poor clinical responses to conventional therapies. Identifying LSC surface markers and targeting LSCs are important for the development of potential therapies. In this study, application of chemotherapy treatment in AML-ETO9a (AE9a) leukemia mice led to the enrichment of a chemotherapy-resistant cell population identified as Lin c-Kit c-MPL . In addition, this c-MPL-positive cell population within Lin c-Kit leukemia cells included a high percentage of cells in a quiescent state, enhanced colony formation ability, and increased homing efficiency. Serial transplantation demonstrated that Lin c-Kit c-MPL cells displayed a significantly high potential for leukemia initiation. Furthermore, it was demonstrated that in AML patients, c-MPL was expressed on the majority of CD34 leukemia cells and that the proportion of c-MPL cells in CD34 leukemia cells is associated with poor prognosis. Finally, AMM2, an inhibitor of c-MPL, was shown to significantly enhance the survival of AE9a leukemia mice when combined with chemotherapeutic agent. These results indicate that c-MPL is a candidate LSC surface marker that may serve as a therapeutic target for the elimination of LSCs. Stem Cells 2018;36:1685-1696.

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Analysis of thrombopoietin receptor (c-mpl) mRNA expression in de novo acute myeloid leukemia

Cited by 12 publications

References 39 publications

Clinical significance of Gata‐1, Gata‐2, EKLF, and c‐MPL expression in acute myeloid leukemia

Clinical significance of Gata‐1, Gata‐2, EKLF, and c‐MPL expression in acute myeloid leukemia

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

c-MPL Is a Candidate Surface Marker and Confers Self-Renewal, Quiescence, Chemotherapy Resistance, and Leukemia Initiation Potential in Leukemia Stem Cells

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