Acute lymphoblastic leukaemia with T- and B-lineage defining markers

Shuyu E; Fatima Z Jelloul; Karen A Nahmod; Nicholas Short; Vasiliki Leventaki; Fuli Jia; Jie Xu; Sanam Loghavi; Wei Wang; L Elias Jabbour; Guilin Tang; L Jeffrey Medeiros; Sa A Wang

doi:10.1016/j.pathol.2025.01.007

Acute lymphoblastic leukaemia with T- and B-lineage defining markers

Pathology. 2025 Apr 2:S0031-3025(25)00126-6. doi: 10.1016/j.pathol.2025.01.007. Online ahead of print.

Authors

Affiliations

¹ Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
² Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³ Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: Swang5@mdanderson.org.

PMID: 40318961
DOI: 10.1016/j.pathol.2025.01.007

Abstract

In acute lymphoblastic leukaemia (ALL), cytoplasmic CD3 (cCD3) is a defining marker for T-lineage, and CD19 plus additional B-cell marker(s) for B-lineage. We identified 23 ALL cases in which the lymphoblasts expressed both cCD3 and CD19, making lineage assignment challenging. These cases represented approximately 10% of cCD3+ ALL and expressed a median of two additional B-cell markers other than CD19, including CD79a (76%), CD22 (22%), PAX5 (57%) and CD10 (44%). Two cases were mixed for T/B-lineage ALL, both positive for BCR::ABL1 rearrangement. In the remaining 21 cases, IgH and/or IgK/L rearrangement were detected in 1 of 19 cases and TRG/TRB in 13 of 21 (62%) cases. Other T-ALL characteristic genetic abnormalities included NOTCH1 mutations (7/21, 33%), PHF6 (6/21, 29%), JAK3 (4/21, 19%), PICALM::MLLT10, TLX3::BCL11B, TRB::HOXA13, SPTAN1::NUP214 and deletion of CDKN2A/CDKN2B. In the 16 cases that demonstrated a T-ALL genetic profile, CD22 (2/16, 13%) was found to be a more specific additional B-lineage marker than CD79a (11/15, 73%), PAX5 (8/14, 57%) or CD10 (7/16, 44%). Our data suggest that mixed T/B-ALL is extremely rare, with most cases associated with BCR::ABL1 and blast crisis of myeloproliferative neoplasms. The majority of cases represent early T-precursor lymphoblastic leukaemia expressing aberrant B-cell markers. We also showed persistent CD19 expression in relapsed/residual disease (16/17, 94%), suggesting its potential role as a therapeutic target and as a marker for detection of residual/relapse disease in these ALL cases.

Keywords: B-cell markers; CD22; IgH; T-lymphoblastic leukaemia; TCR; mixed phenotype acute leukaemia.