Clonal Architecture of ASXL1-mutated Myelofibrosis (CLONEMF)

Prospective study to decipher the clonal architecture of ASXL1-mutated primary and secondary myelofibrosis and its impact on prognosis

The clonal architecture of myelofibrosis patients is still little described. Inconsistent results in terms of the prognostic value of some mutations are observed in the literature, in particular concerning ASXL1 mutations. We assume that a better understanding of the clonal architecture of ASXL1-mutated myelofibrosis could help refining the prognostic impact of ASXL1 mutations. This study aims to evaluate a multicenter cohort of 50 patients. Blood of patients will be collected within 18 months of diagnosis. After 4 years of follow-up of the patient as part of his usual care, data on survival and leukemic transformation will be collected.

Biological: Determination of clonal architecture by sorting of circulating CD34 positive cells followed by cell culture and colony genotyping and/or single-cell DNA-sequencing Secondary outcome: transcriptomic study by RNA-sequencing

The clonal architecture is defined by the number of mutations (numerical), the order of acquisition of the mutations (categorial, pre/post/separated), the mutational branching (categorial, yes/no), the presence of distinct clones (categorial, yes/no) and the transition towards homozygosity of each clone (categorial, yes/no). All parameters of clonal architecture will be analyzed together using a multivariate classification (Factor Analysis for Mixed Data) followed by a clustering which allow us to identify homogeneous cluster of patients.

Description of previously constituted prognostic genomic groups (according to Luque Paz et al. 2021) within identified clusters of clonal architecture

The repartition of patients onto genomic groups will be reported for each clusters of clonal architecture (number and percentage).

Evaluation of overall survival of the patients at 4 years according to their clonal architecture profile

Evaluation of the leukemia-free survival of the patients at 4 years according to their clonal architecture profile

Inclusion Criteria: Adults (age ≥18 years), Affiliated to the national social security system, ASXL1 mutated primary or secondary myelofibrosis, Signed the consent to participate in the study, Included, or consenting to be included, in the national clinical-biological database of France Intergroupe Syndrome Myéloprolifératifs (FIM). Exclusion Criteria: Patient with another active hematological disease or cancer at the time of diagnosis, Person subject to legal protection scheme or incapable of giving consent.