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The T-ALL team, part of the ALL lab at the Josep Carreras Leukaemia Research Institute, makes a step forward to use genomic information to predict response to treatment and outcome of adult T-cell acute lymphoblastic leukaemia patients. Results show that a combination of copy number variations and specific mutations worsens patient survival significantly, while alterations in specific genes would help treatment success. These results support the widespread adoption of genomic and genetic testing in T-ALL patients to better assess their risk and select the best treatment option in a personalised way.
T-cell acute lymphoblastic leukaemia (T-ALL) is an uncommon type of blood cancer characterised by the uncontrolled growth of T-lymphocyte precursors, a component of the immune system, in the bone marrow. T-ALL affects all ages, but survival decreases over time, with very poor prognosis when diagnosed after the age of 50.
The underlying cause of the disease are a series of genetic alterations in the lymphocyte precursors leading to its malignant transformation. Despite many of these alterations have been already described, thanks to the widespread use of genomic tools for research, their clinical impact still remain unclear and current diagnosis heavily rely on morphological and cytogenetic traits.
To offer insights on how genetic testing could make a difference in T-ALL risk assessment, a team of researchers led by Dr. Eulàlia Genescà at the Josep Carreras Leukaemia Research Institute genetically characterized a group of 107 patients and matched it with a set of completed clinical data, comprising treatment option, follow-up and outcome, obtained by the ALL-PETHEMA cooperative group, with which Dr. Genescà is actively cooperating and collaborating. These genetic traits were as diverse as single nucleotide mutations and gains or losses of DNA.
The results of the study, first authored by Dr. Celia González-Gil with the collaboration of the haematology units of several Spanish hospitals, have been published recently in the journal Haematologica. In this work, the group identify the deletion of the “leg” of chromosome 5 (known as del(5q) in genetics terminology), as a new prognostic marker in adult T-ALL. Previously, they had reported also in Haematologica the presence of specific mutations in genes known to be instrumental for T-ALL development (like DNMT3A, N/KRAS, MSH2 or U2AF1), with high impact in the patient’s overall survival. The combination of both types of alterations improves adult T-ALL patient’s classification and their stratification according to risk.
Interestingly, this feature, del(5q), is a known cause for other blood malignancies and has been recently linked to the development of myelodysplastic syndromes, according to a report by Dr. Francesc Solé and Dr. Pamela Acha, also researchers from the Josep Carreras Institute.
Similarly, patients with more than 14 different genetic abnormalities in their cancer cells showed also a poorer overall survival. This seems logical, since every alteration is potentially a door to escape therapy and, therefore, these are the patients reaching the lowest levels of complete remission after treatment.
On the other hand, the analysis revealed that patients with deletions in the CDKN2A and B genes and showing cortical immunophenotype (a cellular trait), had actually good prognosis, with better overall survival rates.
The particularly high heterogeneity of T-ALL had made it very difficult to use genetic information as routine prognosis markers in the past. However, in the light of the new data by Genescà and González-Gil, we are a step closer to developing new personalised treatment pathways for patients, tailored according to the genetic characteristics of their own tumours.
The research in this report has been partly funded by the Spanish Association Against Cancer (AECC), the Spanish Society for Haematology and Haemotherapy (SEHH) and the José Carreras Leukämie-Stiftung. It also received public funds from the EU ERDF/ESF program, the Spanish Government through ISCIII and the Catalan Government through CERCA. No AI tools have been used in the production of this news piece.
