The genetic mechanism of leukemogenesis in adults with B-cell acute lymphoblastic leukemia (B-ALL) is largely unknown, and the clinical result has been disappointing. For a study, researchers sought to get a better knowledge of the biological features of adult B-ALL, enhance disease stratification, and identify molecular targets. The study comprised adolescents and young adults (AYA) (15 to 39 years, n=193) and adults (40 to 64 years old, n=161) with chromosome-negative (Ph) B-ALL. The cohort was classified into specific subgroups using integrated transcriptomic and genomic analysis. About 278 (86.1%) of the 323 patients included in the RNA sequencing analysis were categorized into 18 categories. The ZNF384 subtype was the most common (22.6%), with two novel subtypes (CDX2-high and IDH1/2-mut) discovered among patients not allocated to the recognized subtypes. 

The CDX2-high subtype (3.4%) was distinguished by strong CDX2 expression and recurrent gain of chromosome 1q. IDH1 R132C or IDH2 R140Q mutations with distinct transcriptional and high-methylation patterns characterized the IDH1/2-must subgroup (1.9%). Both subtypes had a dismal prognosis and were regarded as poor prognostic variables regardless of clinical characteristics. When compared to a previously published pediatric B-ALL cohort (n=1003), the rates of these subtypes in AYA/adults were considerably greater than in children. They mapped the genomic and transcriptome landscape of adult B-ALL and discovered two new subgroups that were associated with poor disease outcomes. The findings emphasized the age-dependent distribution of subtypes, which helped to explain why adult and juvenile B-ALL patients have different prognoses.