Study Suggests Link Between Aging, Low-Hypodiploid ALL

By Cecilia Brown - Last Updated: September 20, 2023

A recent study “unveils a link” between aging and low-hypodiploid acute lymphoblastic leukemia (ALL), suggesting that TP53-mutant clonal hematopoiesis represents a “preleukemic reservoir that can give rise to aneuploidy and B-[cell] ALL.”

Rathana Kim, PharmD, of Université Paris Cité, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U944, and the Hôpital Saint-Louis, and colleagues conducted the study and published their findings in Blood Cancer Discovery.

Dr. Kim and colleagues conducted the research to investigate the genomic base of low-hypodiploid ALL in adults because low hypodiploidy “defines a rare subtype” of B-cell ALL with a “dismal outcome.”

They analyzed copy-number aberrations, loss of heterozygosity, mutations, and cytogenetics data in a prospective cohort of 591 adult patients with Philadelphia (Ph)-negative B-cell ALL, identifying 80 cases (14%) of low-hypodiploid ALL.

“Genomic analysis was critical for evidencing low hypodiploidy in many cases missed by cytogenetics,” Dr. Kim and colleagues wrote.

They found that the proportion of low-hypodiploid ALL within Ph-negative B-cell ALL “dramatically increased with age.” The proportion was 3% in patients under 40 years old and was 32% in the patients over 55 years old. Somatic TP53 biallelic inactivation was the “hallmark” of adult low-hypodiploid ALL, as it was detected in 98% of cases.

“Strikingly, we detected TP53 mutations in post-treatment remission samples in 34% of patients,” Dr. Kim and colleagues wrote. “Single-cell proteogenomics of diagnosis and remission bone marrow samples evidenced a preleukemic, multilineage, TP53-mutant clone, reminiscent of age-related clonal hematopoiesis.”


Kim R, Bergugnat H, Larcher L, et al. Adult low-hypodiploid acute lymphoblastic leukemia emerges from preleukemic TP53-mutant clonal hematopoiesis. Blood Cancer Discov. 2023;4(2):134-149. doi:10.1158/2643-3230.bcd-22-0154

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