If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Gain of extra copies of the 5′ portion of the PAX5 gene (PAX5-partial tandem duplication
or PAX5-PTD) has been proposed to define a specific genetic subgroup of B-ALL (PMID:
30842609), and has most recently been associated with the novel PAX5-alteration driven
(PAX5alt) subtype of the disease (PMID: 30643249). We determined the incidence and
clinical, morphologic and molecular correlations of PAX5-PTD in an unselected cohort
of 228 B-ALL patients. PAX5-PTD was detected by Chromosomal microarray (CMA) analysis
in 5/228 B-ALLs (2.1%). There were two extra copies (triplication) of a 38-51 kb region
(exons 2-5), encoding the PAX5 DNA-binding domain. The triplications were 'in frame',
predicted to result in an altered protein. Two PAX5-PTD cases were classified as Ph-like/CRLF2
positive, based on P2RY8-CRLF2 fusions and JAK mutations detected by NGS panel testing.
Notably, occurrence of PAX5-PTD in CRLF2-positive B-ALL has been reported previously.
Extensive genetic evaluation of the remaining three PAX5-PTD cases excluded other
subtype-defining genetic drivers; the cases were positive for CDKN2A/2B deletions
(3/3), IKZF1 loss (2/3), RAS pathway and epigenetic mutations, and negative for abnormalities
of the second PAX5 allele. Clinically, 4/5 patients presented at a young age (<5 years),
2 with standard-risk (SR), and 3 with high-risk (HR) B-ALL. One patient with SR and
one with HR ALL developed early relapse. Our findings suggest that, similar to other
PAX5 alterations, PAX5-PTD acts both as the primary driver in PAX5alt B-ALL, as well
as the secondary abnormality enriched in Ph-like/CRLF2 positive B-ALL cases.
To read this article in full you will need to make a payment