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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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

Spots Global Cancer Trial Database for next generation sequencing (dna and rna)