Therapy-related Acute Lymphoblastic Leukaemia has a Unique Genetic Profile Compared to De Novo Acute Lymphoblastic Leukaemia

Abstract

Background: Unlike therapy-related myeloid neoplasms, therapy-related acute lymphoblastic leukaemia (tr-ALL) is poorly defined due to its rarity. However, increasing reports have demonstrated that tr-ALL is a distinct entity with adverse genetic features and clinical outcomes. Methods: We compared the clinicopathological characteristics and outcomes of patients diagnosed with tr-ALL (n = 9) or de novo ALL (dn-ALL; n = 162) at a single institution from January 2012 to March 2021. The mutational landscapes of eight tr-ALL and 63 dn-ALL patients were compared from a comprehensive next-generation sequencing panel. Results: All tr-ALL patients had the B-cell phenotype. The most frequently mutated genes were IKZF1 (37%), CDKN2A (14%), SETD2 (13%), and CDKN2B (11%) in dn-ALL, whereas TP53 (38%) and RB1 (25%) mutations were most common in tr-ALL. tr-ALL patients did not show a statistically significant difference in overall survival (p = 0.70) or progression-free survival (p = 0.94) compared to dn-ALL patients. Conclusions: In this study, we determined the clinical and genetic profiles of Korean patients with tr-ALL. We found alterations in genes constituting the TP53/RB1 pathway are more frequent in tr-ALL. Due to the rarity of the disease, multi-institutional studies involving a larger number of patients are required in future study.

A case report of secondary B-cell acute lymphoblastic leukemia treated with a combination of FLT3 inhibitor and decitabine

“…Compared to newly diagnosed ALL (dn ALL), the occurrence of high-risk cytogenetic and molecular features is higher in t-ALL. These features include BCR::ABL1 positivity, MLL rearrangements, and hyperdiploid (3,7,11,12). Several studies have also indicated that the incidence of BCR::ABL1 positivity is similar between these two types of leukemia (3,13).…”

“…These features include BCR::ABL1 positivity, MLL rearrangements, and hyperdiploid (3,7,11,12). Several studies have also indicated that the incidence of BCR::ABL1 positivity is similar between these two types of leukemia (3,13). The most commonly mutated genes in dn ALL were IKZF1 (37%), CDKN2A (14%), SETD2 (13%), and CDKN2B (11%).…”

Comprehensive insights into AML relapse: genetic mutations, clonal evolution, and clinical outcomes

“…NGS data analysis was carried out using the DxSeq analyzer (Dxome). Single-nucleotide variants, small insertions and deletions, and copy number variants were detected using established methods [ 18 , 19 ]. Variant allele frequency (VAF) represents the proportion of sequence reads that align with a particular DNA variant, divided by the total coverage observed at that specific genomic location.…”

Unraveling trajectories from aplastic anemia to hematologic malignancies: genetic and molecular insights

“…NGS data analysis was conducted using a DxSeq analyzer (Dxome). Single-nucleotide variants, small insertions and deletions, and copy number variants were identified according to previously described methods ( 18 , 19 ). Confirmation of germline variant was achieved with NGS results using skin fibroblast analysis.…”