Immature Immunoglobulin Gene Rearrangements Are Recurrent in B Precursor Adult Acute Lymphoblastic Leukemia Carrying TP53 Molecular Alterations

Abstract

Here, we describe the immunoglobulin and T cell receptor (Ig/TCR) molecular rearrangements identified as a leukemic clone hallmark for minimal residual disease assessment in relation to TP53 mutational status in 171 Ph-negative Acute Lymphoblastic Leukemia (ALL) adult patients at diagnosis. The presence of a TP53 alterations, which represents a marker of poor prognosis, was strictly correlated with an immature DH/JH rearrangement of the immunoglobulin receptor (p < 0.0001). Furthermore, TP53-mutated patients were classified as pro-B ALL more frequently than their wild-type counterpart (46% vs. 25%, p = 0.05). Although the reasons for the co-presence of immature Ig rearrangements and TP53 mutation need to be clarified, this can suggest that the alteration in TP53 is acquired at an early stage of B-cell maturation or even at the level of pre-leukemic transformation.

Insights into IGH clonal evolution in BCP-ALL: frequency, mechanisms, associations, and diagnostic implications

“…First, we herein only studied clonal evolution in the IGH locus, but a study on clonal evolution of T-cell receptors might allow deeper insights - particularly as the TRD locus has shown similar recombinase activity as the IGH locus in patients with V H replacement ( 47 ). Second, a recent study has shown that BCP-ALL harboring TP53 alterations are associated with immature DJ H rearrangements ( 48 ). Assuming that TP53 alterations occur already in the pre-leukemic cell compartment, one should study if these cases show clonal evolution rates similar to KMT2A -rearranged cases.…”