Dataset Information

A new signaling cascade linking BMP4, BMPR1A, ?Np73 and NANOG impacts on stem-like human cell properties and patient outcome.

ABSTRACT: In a significant number of cases cancer therapy is followed by a resurgence of more aggressive tumors derived from immature cells. One example is acute myeloid leukemia (AML), where an accumulation of immature cells is responsible for relapse following treatment. We previously demonstrated in chronic myeloid leukemia that the bone morphogenetic proteins (BMP) pathway is involved in stem cell fate and contributes to transformation, expansion, and persistence of leukemic stem cells. Here, we have identified intrinsic and extrinsic dysregulations of the BMP pathway in AML patients at diagnosis. BMP2 and BMP4 protein concentrations are elevated within patients' bone marrow with a BMP4-dominant availability. This overproduction likely depends on the bone marrow microenvironment, since MNCs do not overexpress BMP4 transcripts. Intrinsically, the receptor BMPR1A transcript is increased in leukemic samples with more cells presenting this receptor at the membrane. This high expression of BMPR1A is further increased upon BMP4 exposure, specifically in AML cells. Downstream analysis demonstrated that BMP4 controls the expression of the survival factor ?Np73 through its binding to BMPR1A. At the functional level, this results in the direct induction of NANOG expression and an increase of stem-like features in leukemic cells, as shown by ALDH and functional assays. In addition, we identified for the first time a strong correlation between ?Np73, BMPR1A and NANOG expression with patient outcome. These results highlight a new signaling cascade initiated by tumor environment alterations leading to stem-cell features and poor patients' outcome.

SUBMITTER: Voeltzel T

PROVIDER: S-EPMC6160490 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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A new signaling cascade linking BMP4, BMPR1A, ΔNp73 and NANOG impacts on stem-like human cell properties and patient outcome.

Voeltzel Thibault T Flores-Violante Mario M Zylbersztejn Florence F Lefort Sylvain S Billandon Marion M Jeanpierre Sandrine S Joly Stéphane S Fossard Gaelle G Milenkov Milen M Mazurier Frédéric F Nehme Ali A Belhabri Amine A Paubelle Etienne E Thomas Xavier X Michallet Mauricette M Louache Fawzia F Nicolini Franck-Emmanuel FE Caron de Fromentel Claude C Maguer-Satta Véronique V

Cell death & disease 20180927 10

In a significant number of cases cancer therapy is followed by a resurgence of more aggressive tumors derived from immature cells. One example is acute myeloid leukemia (AML), where an accumulation of immature cells is responsible for relapse following treatment. We previously demonstrated in chronic myeloid leukemia that the bone morphogenetic proteins (BMP) pathway is involved in stem cell fate and contributes to transformation, expansion, and persistence of leukemic stem cells. Here, we have ...[more]

PMID: 30262802

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Project description:BackgroundThe management of diabetes is complex. There is growing recognition of the use of patient-reported outcome measures (PROMs) as a standardized method of obtaining an outlook on patients' functional status and well-being. However, no systematic reviews have summarized the studies that investigate the measurement properties of diabetes PROMs.ObjectiveOur aims were to conduct a systematic review of studies investigating the measurement properties of diabetes PROMs by evaluating the methodological quality and overall level of evidence of these PROMs and to categorize them based on the outcome measures assessed.MethodsThis study was guided by the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. Relevant articles were retrieved from the Embase, PubMed, and PsychINFO databases. The PROMs were evaluated with the COSMIN (COnsensus-based Standards for the selection of health Measurement Instruments) guidelines.ResultsA total of 363 articles evaluating the measurement properties of PROMs for diabetes in the adult population were identified, of which 238 unique PROMs from 248 studies reported in 209 articles were validated in the type 2 diabetes population. PROMs with at least a moderate level of evidence for ≥5 of 9 measurement properties include the Chinese version of the Personal Diabetes Questionnaire (C-PDQ), Diabetes Self-Management Instrument Short Form (DSMI-20), and Insulin Treatment Appraisal Scale in Hong Kong primary care patients (C-ITAS-HK), of which the C-PDQ has a "sufficient (+)" rating for >4 measurement properties. A total of 43 PROMs meet the COSMIN guidelines for recommendation for use.ConclusionsThis study identified and synthesized evidence for the measurement properties of 238 unique PROMs for patients with type 2 diabetes and categorized the PROMs according to their outcome measures. These findings may assist clinicians and researchers in selecting appropriate high-quality PROMs for clinical practice and research.Trial registrationPROSPERO International Prospective Register of Systematic Reviews CRD42020180978; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020180978.

Dataset Information

A new signaling cascade linking BMP4, BMPR1A, ?Np73 and NANOG impacts on stem-like human cell properties and patient outcome.

Publications

A new signaling cascade linking BMP4, BMPR1A, ΔNp73 and NANOG impacts on stem-like human cell properties and patient outcome.

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