A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics

Abstract

BCR-ABL1-like B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly characterized in adults. We sought to establish the frequency and outcome of adolescent and adult BCR-ABL1-like ALL using a novel RNA-Seq signature in a series of patients with BCP-ALL. To this end, we developed and tested an RNA-Seq custom panel of 42 genes related to a BCR-ABL1-like signature in a cohort of 100 patients with BCP-ALL and treated with risk-adapted ALL trials. Mutations related to BCR-ABL1-like ALL were studied in a panel of 33 genes by next-generation sequencing (NGS). Also, CRLF2 overexpression and IKZF1/CDKN2A/B deletions were analyzed. Twenty out of 79 patients (12-84 years) were classified as BCR-ABL1-like (25%) based on heatmap clustering, with significant overexpression of ENAM, IGJ, and CRLF2 (P ≤ 0.001). The BCR-ABL1-like subgroup accounted for 29% of 15-60-year-old patients, with the following molecular characteristics: CRLF2 overexpression (75% of cases), IKZF1 deletions (64%), CDKN2A/B deletions (57%), and JAK2 mutations (57%). Among patients with postinduction negative minimal residual disease, those with the BCR-ABL1like ALL signature had a higher rate of relapse and lower complete response duration than non-BCR-ABL1-like patients (P = 0.007). Thus, we have identified a new molecular signature of BCR-ABL1-like ALL that correlates with adverse prognosis in adult patients with ALL.

Clinical application of whole transcriptome sequencing for the classification of patients with acute lymphoblastic leukemia

“…Recently, a targeted RNA-Seq panel of 38 genes was published to identify adult BCP-ALL pts. with BCR - ABL1 -like characteristics [ 37 ]. The application of this gene panel identified 30 BCR-ABL1 -like cases, of which 28 (93%) were concordant with the group classification, by the list of 26 genes.…”

“…The majority of the genes (65%) were also present in the recently published list of a targeted RNA-Seq panel [ 18 ], resulting in an overlap of 93% in classification results. We only characterized 13% of our BCP-ALL cohort as BCR - ABL1 -like cases, which is below the typical range of 24–33% [ 37 , 51 , 52 ]. However, 67% of the patients from our BCP ALL cohort fall into the adult or elderly age group, and it has been shown that the frequency of BCR - ABL1 -like cases declines with age, with an incidence just of between 7 and 20% for adults and elderly patients [ 53 , 54 ].…”

ENAM gene associated with T classification and inhibits proliferation in renal clear cell carcinoma

“…However, in some tumors, ENAM exhibits extraordinary expression patterns and is possibly involved in the disease progression. For instance, Sanchez and their colleagues identified the overexpression character of ENMA based on a cohort of 100 B-cell precursors from patients with acute lymphoblastic leukemia; this feature may lead to poor prognosis [ 26 ]. To date, the role of ENAM in ccRCC has not been reported.…”

Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblastic leukemia

“…The Ph-like subtype is BCR-ABL1 negative, but its gene expression feature is similar to that of BCR-ABL1-positive patients [89][90][91][92][93]. The Ph-like subtype was registered in the 2016 revision to the WHO classification of myeloid neoplasms and acute leukemia [19].…”