Refined Leukemia Classification Is Expected To Improve Diagnosis


With the discovery of multiple new subtypes of B-cell acute lymphoblastic leukemia (B-ALL), investigators are expecting to make both the diagnosis and treatment of high-risk patients more efficient. Researchers from St. Jude Children’s Research Hospital published their study in the latest edition of Nature Genetics.

The team identified 23 B-ALL subtypes, including eight completely individual forms, each with distinct genomic and clinical features as well as outcomes. This means that more than 90 percent of all B-All cases can now be categorized by subtype, compared to 70 percent a few years ago.


B-ALL has remarkable molecular diversity, which we and others have used to refine classification and drive the development of precision medicines to improve B-ALL treatment and outcomes”, noted corresponding author Charles Mullighan, MBBS, M.D. “Part of precision medicine is an accurate molecular diagnosis, which this study provides to more patients”.

Alterations to the PAX5 gene led to the formation of two groups, including PAX5 P80R, as the first lymphoblastic leukemia activated by a point mutation. Tests showed that this strand “impairs development of B lymphoid cells and promotes development of B-ALL”.

PAX5-altered was characterized by diverse alterations in the gene, including sequence mutations or rearrangements with one of 24 other genes. Overall, the PAX5 subtypes account for almost 10 percent of the previously uncategorized cases of B-ALL.

The study confirmed the theory that RNA sequencing can help identify multiple types of genomic alterations and reaffirmed the benefits of using this technique for leukemia diagnosis, especially when whole-genome sequencing is not possible.

As a clinician, these data describing the diversity of subtypes of B-ALL will allow us to refine our prognostic abilities for individual patients, and ultimately, will lead to the development of new targeted therapies that will more effectively treat the leukemia with fewer side effects”, added Mark Litzow, M.D, co-author and chair of the Leukemia Committee for Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network.

Other subtypes include NUTM1 gene rearrangement with different partner genes, which appears to be vulnerable to treatment; HLF gene rearrangement to multiple genes, including TCF4; three subtypes for ETV6-RUNX1, KMT2A, and ZNF384 groups.

Having a better classification when it comes to these subtypes will naturally translate into improved tailor-made treatments and higher levels of patient care.