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Immature Immunoglobulin Gene Rearrangements Are Recurrent in B Precursor Adult Acute Lymphoblastic Leukemia Carrying 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 mutational status in 171 Ph-negative Acute Lymphoblastic Leukemia (ALL) adult patients at diagnosis. The presence of a alterations, which represents a marker of poor prognosis, was strictly correlated with an immature DH/JH rearrangement of the immunoglobulin receptor ( < 0.0001). Furthermore, -mutated patients were classified as pro-B ALL more frequently than their wild-type counterpart (46% vs. 25%, = 0.05). Although the reasons for the co-presence of immature Ig rearrangements and mutation need to be clarified, this can suggest that the alteration in is acquired at an early stage of B-cell maturation or even at the level of pre-leukemic transformation.

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References
1.
Kanagal-Shamanna R, Jain P, Takahashi K, Short N, Tang G, Issa G . TP53 mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper-CVAD-based regimens. Cancer. 2017; 123(19):3717-3724. PMC: 5689475. DOI: 10.1002/cncr.30810. View

2.
Salmoiraghi S, Rambaldi A, Spinelli O . TP53 in adult acute lymphoblastic leukemia. Leuk Lymphoma. 2017; 59(4):778-789. DOI: 10.1080/10428194.2017.1344839. View

3.
Cave H, van der Werff Ten Bosch J, Suciu S, Guidal C, Waterkeyn C, Otten J . Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. European Organization for Research and Treatment of Cancer--Childhood Leukemia Cooperative Group. N Engl J Med. 1998; 339(9):591-8. DOI: 10.1056/NEJM199808273390904. View

4.
Cavagna R, Guinea Montalvo M, Tosi M, Paris M, Pavoni C, Intermesoli T . Capture-based Next-Generation Sequencing Improves the Identification of Immunoglobulin/T-Cell Receptor Clonal Markers and Gene Mutations in Adult Acute Lymphoblastic Leukemia Patients Lacking Molecular Probes. Cancers (Basel). 2020; 12(6). PMC: 7352935. DOI: 10.3390/cancers12061505. View

5.
Bruggemann M, Raff T, Flohr T, Gokbuget N, Nakao M, Droese J . Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2005; 107(3):1116-23. DOI: 10.1182/blood-2005-07-2708. View