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This Study Aims to Improve the Stratification of Patients With Acute Myeloid Leukemia to Enable More Personalized and Effective Treatments, and to Identify and Functionally Validate, at the Single-cell Level, Biomarkers That Can Predict Response to Venetoclax.
Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Summary
The current classification of acute myeloid leukemias (AML) includes more than 20 different diseases, grouped based on their distinctive genomic characteristics, which reflect substantial heterogeneity. The rationale underlying this project is the idea that an effective diagnostic process and functional dissection of transcriptional heterogeneity at the single-cell level will lead to the identification of cell-intrinsic or cell-extrinsic biomarkers of response to novel therapies in order to improve patient care. In particular, with the study we present here, we intend to obtain data relating to the sub-classification of patients into genomic subgroups with biological and prognostic relevance. Genomic subgroups are categories into which patients affected by the same disease can be divided based on the genetic characteristics found in each patient. The study foresees that part of the biological sample, collected through bone marrow blood sampling, already provided for by clinical practice will be subjected to further analyses. Specifically, DNA and RNA sequencing analyses will be performed on the cells that will be isolated from the bone marrow blood. The objective is to search for molecular markers that may allow better biological and prognostic classification of patients. Molecular markers are particular DNA sequences that, in our study, would enable the classification of patients into subgroups.
Official title: Analisi Geno-trascrittomica Dell'eterogeneità Clonale Nella Leucemia Mieloide Acuta a Livello di Singola Cellula: Implicazioni Per la Diagnosi e la Risposta al Trattamento Con Venetoclax
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
INTERVENTIONAL
Enrollment
420
Start Date
2022-05-10
Completion Date
2030-12
Last Updated
2026-10-14
Healthy Volunteers
No
Conditions
Interventions
Bulk genotyping of AML samples at diagnosis and relapse, scRNA analysis at diagnosis, scRNAseq and genotyping analysis at day 28 after therapy, spatial transcriptomic analysis at day 0 and 28
This intervention enrolls \~420 patients to investigate AML through multi-level genomic and transcriptomic analysis. Bone marrow samples are collected at diagnosis, relapse, and day 28 of treatment. All patients undergo bulk NGS genotyping using a 69-gene panel. Forty patients receiving venetoclax are selected for detailed single-cell RNAseq analysis (\~5000 cells) to dissect cellular heterogeneity, identify blast populations, assess microenvironment composition, and predict cell states via RNA velocity. Four patients undergo spatial transcriptomic analysis (Xenium) on bone marrow biopsies at diagnosis and day 28 to evaluate RNA expression within tissue architecture. This comprehensive approach enables identification of genomic/transcriptomic features associated with treatment response, chemoresistance mechanisms, and personalized targeted treatment markers in heterogeneous AML populations.
Locations (1)
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Haematology Unit
Milan, Italy