Impact of Optical Genome Mapping in Acute Myeloblastic Leukemia

Overview

A retrospective study using a new technology will be performed: the Optical Genome Mapping (OGM) on acute myelogenous leukemia (AML) samples stored at the CRB-Cancer of the Bordeaux University Hospital and annotated in the DATAML clinical database. The main objective is to estimate the proportion of AML patients for whom OGM detects at least one additional abnormality compared to conventional techniques. This study will constitute an important step in the validation of COA as a reference technique for cytogenetic analysis in AML, replacing the classical techniques, and could also constitute a first argument for redesigning the prognostic classification of AML.

In AML prognostic classifications, such as the ELN 2017 classification, which are used to guide treatment choices in the majority of protocols, rely heavily on genetic abnormalities. The Optical Genome Mapping (OGM) is a new technology that combines in one and the same technique the results of karyotype, FISH and SNP-Array, the latter being very little used in current practice in AML. OGM with greater sensitivity and a better resolution than the usual techniques should therefore allow us to identify more abnormalities than conventional cytogenetics; we would then like to determine whether these additional abnormalities have a prognostic impact, i.e., whether they lead to reclassification of patients initially classified as "favorable" or "intermediate" into the "unfavorable" prognostic category, with therapeutic consequences. A retrospective study using the OGM is will be performed on samples stored at the CRB-Cancer of the Bordeaux University Hospital and annotated in the DATAML clinical database. In an original way, the focus will be on AML patients in whom 1 to 3 chromosomal abnormalities (non-recurrent WHO, not related to an unfavourable prognosis) have already been demonstrated by classical techniques, making the hypothesis that it is in this population that we would more easily have patients who could fall into the definition of the complex karyotype and thus into the unfavourable risk category. OGM should therefore reveal a greater number of abnormalities which would allow a better definition of karyotypes with abnormalities, the number of complex and/or monosomal karyotypes and a better stratification of the prognosis of these patients with AML. This is an applied translational research study based on innovative technology that will define the place of OGM over current techniques used in the initial management of AML patients, and it may well become the new standard for cytogenetic analysis of AML in the coming years.