Role of BMP Pathway in MDS Progression

Официальное название

Role of the BMP Pathway in Myelodysplastic Syndromes Progression and in the Transition to Acute Myeloid Leukemia

Обзор

Myelodysplastic syndromes (MDS) are hematological cancers that can progress to acute myelogenous leukemia (AML). The involvement of the microenvironment in the maintenance, resistance and evolution of MDS is increasingly described. The Bone Morphogenetic Protein (BMP) pathway is involved in numerous functions, including self-renewal of the hematopoietic stem cell compartment and the regulation of hematopoiesis, via interaction with bone marrow stromal cells. Investigators have demonstrated its involvement in chronic myeloid leukemia (CML) and AML, in particular via the activation of TWIST1, ΔNp73, NANOG; it is responsible for an increased state of quiescence of certain cancer stem cells and their resistance. Preliminary results based on the analysis of large databases suggest that the BMP pathway is also altered early in MDS. This study explores the alteration of this pathway in MDS and its involvement in the transformation into AML. If appropriate, the BMP pathway could constitute a very promising therapeutic target to combat transformation into AML.

Вмешательства

• Биопрепарат Collection of EDTA (disodium salt of ethylenediaminetetraacetic acid) tubes of marrow during routine care
  When bone marrow is collected as part of a patient's care (diagnosis, follow-up, suspected AML/MDS hemopathy), one or two additional EDTA tubes of marrow are collected. Certain hematological data (NFP, genetic and molecular characteristics) will be collected in anonymized form and correlated with the BMP pathway alterations measured.

Первичные конечные точки

• Descriptive analysis of the BMP pathway : Bone marrow plasma BMP2/BMP4 levels [Срок оценки: at diagnosis, at 6 months, at 5 years]
• Descriptive analysis of the BMP pathway : Bone marrow mononuclear cell fraction [Срок оценки: at diagnosis, at 6 months, at 5 years]
• Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Functional level [Срок оценки: at diagnosis, at 6 months, at 5 years]
• Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Transcriptomic level [Срок оценки: at diagnosis, at 6 months, at 5 years]
• Descriptive analysis of the BMP pathway : - Bone marrow mesenchymal stem cells number and differentiation capacities after passage 0 - Protein level [Срок оценки: at diagnosis, at 6 months, at 5 years]

Критерии участия

Критерии включения

• Adult patients with myelodysplastic syndrome or suspected myelodysplastic syndrome according to the criteria defined by the World Health Organization Or
• Adult patient with suspicion of de novo acute myeloid leukemia at initial treatment

Критерии исключения

• Frontier MDS/myeloproliferative syndromes including chronic myelomonocytic leukemia
• MDS and AML having already benefited from cytotoxic treatment including hydroxycarbamide, azacytidine, intensive chemotherapy
• Patients objecting to their inclusion in the study
• Pregnant or breastfeeding women
• Patients under legal protection measure

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 1 центр

• Hospices Civils de Lyon — Lyon

Идентификаторы

NCT: NCT06175923 · 69HCL22_0491

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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