Ph-like B-ALL is relatively common, with a prevalence of 10-25% in patients with ALL.
The clinical and morphologic features in patients diagnosed with Ph-like B-ALL are in general similar to those seen in other types of ALL, although presentation with an elevated white blood cell count is one of the high-risk clinical features that tend to be more common in this subset.
Ph-like/BCR-ABL1-like B-ALL was independently described by two groups as a subtype of ALL that had a gene expression profile very similar to that of Ph-like ALL, a high frequency of deletions of IKZF1 (which codes for the lymphoid transcription factor, IKAROS), and of other lymphoid transcription factor genes, such as PAX5 and EBF1, and an overall poor survival [5, 6].
In contrast, high risk Ph-like B-ALL patients with CRLF2/JAK pathway lesions are eligible for the AALL1521 trial which combines post-induction therapy with ruxolitinib .
The testing algorithm developed by the MD Anderson trial for Ph-like B-ALL involves screening all newly diagnosed or relapsed B-ALL patients for CRLF2 expression by flow cytometry; BCR-ABL1 translocation by FISH/PCR; and for gene copy number analysis by MLPA/SNP microarray.
The study used the clonoSEQ assay and University of Washington's flow cytometry assay to detect the primary cancer clone in pre-treatment bone marrow samples and track the cancerous clone in bone marrow samples obtained from 99 patients with B-ALL at Day 29 post-chemotherapy treatment.
These findings show the enhanced accuracy and sensitivity of clonoSEQ, and the potential need to redefine detection thresholds for MRD to improve the way patients with B-ALL are monitored during and post-treatment, said Dr.
Our work is motivated by a lack of information on the genetic basis of many B-ALL cases, said corresponding author Charles Mullighan, M.B.B.S., M.D., a member of the St.
The researchers studied a group of 1,913 patients who had B-ALL to understand the subtypes genetic basis.
Our work revealed that in this type of B-ALL there is a sequence of molecular events that involves the interplay of two transcription factors, Mullighan said.
The genomic landscape of this subtype of B-ALL can also be visualized using ProteinPaint (pecan.stjude.org), a powerful interactive tool developed at St.
Co-author Stephen Hunger, M.D., chief of the Division of Oncology at the Childrens Hospital of Philadelphia, said the genetic defects underlying this relatively common subset of B-ALL were not fully understood before discovery of the DUX4 abnormalities.