Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Myeloid Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Targeted Next Generation Sequencing (DNA and RNA)

Next Generation Sequencing (DNA and RNA)

Stéphanie DULUCQ

Treatment of chronic myeloid leukemia (CML) has been revolutionized by tyrosine kinase inhibitor (TKI). Nevertheless, case of failure and suboptimal response are still observed even in children. Pediatric CML is a rare disease and differs from adult in terms of disease presentation and treatment response underlying a likely different CML biology. Molecular mechanisms that induce resistance to TKI are still poorly characterized except mutations in the tyrosine kinase domain of BCR::ABL1. We propose to search for a molecular signature to predict the response to TKI in the pediatric population.

Commonly mutated genes associated with myeloid malignancies have been described in acceleration phase and blastic phase but also at diagnostic in adult chronic phase-CML (CP-CML). The impact of these mutations on treatment response is still debated but several studies observed a worse outcome in adult patients with some mutations. In children only one study explored the molecular status of 30 genes in 21 children and young adults. They found a higher proportion of ASXL1 mutations in children than in adult They did not observed any significant difference in overall survival of ASXL1 mutated versus non-mutated patients but probably due the small size of the cohort. We propose here, to investigate retrospectively on DNA at diagnosis of 88 CP-CML children the mutation status of 64 genes by next generation sequencing and to see if there is an association with the response to TKI treatment. We will complete the molecular signature by analyzing the differentially genetic expression profile by RNA-seq on peripheral blood RNA of 8 patients with CCR at 12 months (and/or a BCR ::ABL1 IS ≤1%IS) and 8 patients with no CCR at 12 months.

CML Pediatric ITK Response According to Molecular Identification at Diagnosis

CML Pediatric ITK Response According to Molecular Identification at Diagnosis (CML Piramid

We will analyse the impact of the presence of mutations on the obtention of CCR

We will analyse the impact of the presence of mutations on the obtention of molecular response (MR4, MMR)

We will analyse the impact of the presence of mutations on the type of response

We will analyse the impact of the presence of mutations on the occurrence of loss of complete hematologic, and/or cytogenetic and/or molecular responses

We will analyse the impact of the presence of mutations on the occurrence of mutation in the TK domain ABL1

Progression to accelerated phase or blast crisis and deaths will be analysis according to the mutational status

We will analyse the impact of the presence of mutations on OS

University Hospital, Bordeaux

Skin and Connective Tissue Diseases

Heart and Blood Diseases

Breast Neoplasms

Cardiac Complexes, Premature

Breast Diseases

Skin Diseases

Conventional treatment protocols of breast cancer

Anne-Cécile PHILIPPE, Dr

Emmanuelle JACQUET, Dr

Anne-Cécile PHILIPPE, Pr

Emmanuelle JACQUET

Mireille MOUSSEAU, Pr

Candidate markers have been identified thanks to an original approach developed by our research team aiming at detecting ectopic gene expression using public pan-genomic breast cancer data. The same approach had already been used and validated in lung tumors, leukemias and lymphomas. The main objective of the present research is to use tumor samples from patients in a retrospective and prospective cohort to test and validate the relevance of these prognostic markers in breast cancer.

Following a diagnosis of breast cancer, the most immediate challenges in patient management are the determination of prognosis and the identification of the most appropriate neoadjuvant and adjuvant systemic therapy. Indicators to assess the risk of relapse or metastasis during treatment are still largely insufficient, a situation which does not allow to precisely adjust the treatment, often leading to heavy side effects. In order to minimize the side effects and risks of therapies, it is therefore necessary to discover new markers which would enable us to reliably assess the prognosis of patients diagnosed with breast cancer.

The approach used here for discovering new prognostic markers is based on an original strategy developed by the researchers associated with this project and published in the respective contexts of lung cancer, acute lymphoblastic leukemia and lymphoma. Indeed, genetic abnormalities and deregulation of the systems controlling the expression of specific gene programs not only lead to the abnormal extinction of normally active genes, but is also responsible for the aberrant activation of genes that normally should remain silent. The investigators have recently demonstrated that any type of malignancy is associated with the ectopic expression of these normally silent genes, including genes of the male germline. The in-depth study of these aberrant gene expressions and the search for correlations and associations with the clinical and biological data of the tumors show that the expression of some of these genes and the presence of their products are good indicators of tumor aggressiveness.

The investigators propose here to apply the same approach for the search for new prognostic markers in the case of breast cancer. A prior analysis of breast tumors, of which transcriptome data are publicly available, has identified a number of tissue-specific genes, including the germline and placenta genes, frequently activated in breast cancer. Based on our past observations, our hypothesis is that some of them may directly reflect the level of tumor aggressiveness and could therefore be used as prognostic biomarkers.

The objective of this work will be to look for the prognostic value of these genes by using the samples collected in this cohort of patients to detect their activation and to correlate these aberrant activations with the anatomopathological data of the tumor, as well as to the clinico-biological data and patient follow-up.

The research uses blood samples and biopsies made at diagnosis or during surgical resection of the tumor for gene or protein expression analysis (RNA and protein extraction).

Identification of New Prognostic Markers for Breast Cancer.

Identification de Nouveaux Marqueurs Pronostiques Des Cancers du Sein

The overall survival and disease-free survival of patient with breast cancers will be analyzed in terms of gene expression change in order to identify new prognostic biomarkers.

Evaluation of a response rate after neoadjuvant chemotherapy according to RECIST criteria

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CML Pediatric ITK Response According to Molecular Identification at Diagnosis	NCT05605379	Chronic Myeloid...	Next Generation...	6 Years - 18 Years	University Hospital, Bordeaux
CML Pediatric ITK Response According to Molecular Identification at Diagnosis	NCT05605379	Chronic Myeloid...	Next Generation...	6 Years - 18 Years	University Hospital, Bordeaux
Identification of New Prognostic Markers for Breast Cancer.	NCT03436069	Breast Cancer	Conventional tr...	18 Years -	University Hospital, Grenoble

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