Molecular Predictors of Treatment Failure in ALK-Negative Anaplastic Large T-Cell Lymphoma

ALK-negative anaplastic large T-cell lymphoma (ALK-negative ALTCL) is a rare aggressive disease, constituting 12% of all T-cell lymphomas of adults. When using CHOP/CHOEP chemotherapy overall and event-free survival is less than 50%. Factors of poor prognosis include IPI (3-5), CNS and skin involvement as well as molecular predictors.

The aim of current study was to detect rearrangements (R) of DUSP22 gene, t(6;7)(p25.3;q32.3), inv(3)(q26q28), involving TP63 gene using fluorescence in situ hybridization and ТР63 mutation by Sanger sequencing.

23 patients with ALK-negative ALTCL were involved in current study: 14 males, 9 females. Advanced stage of disease was diagnosed in 70 % of patients. All patients were treated with high-dose chemotherapy.

In 20% of patients were revealed DUSP22-R, 13% - TP63 abnormalities, 67% of patients were triple-negative (without ALK-R, DUSP22-R, TP63-R).

There weren't detected any mutations in DNA-binding domain of TP63 gene.

Comparing data of molecular studies and clinical data it was revealed that presence or absence of above-mentioned gene rearrangements did not affect disease stage: III stage was diagnosed in 30% of cases with DUSP22-R and in 33% of triple-negative cases, IV stage in 100% cases with TP63-R, in 67% with DUSP22-R, in 40% with triple-negative variant. Majority of patients had IPI (3-5) in all three cytogenetic groups. In 100% of cases with DUSP22-Rwere revealed more than 2 extranodal site of involvement.

Overall (OS) and progression-free survival (PFS) depending on molecular profile were 100% and 100%, respectively, in case with DUSP22-R. In case of TP63-R OS and PFS were 8% and 10%, respectively, in triple-negative cases - 60% and 39%, respectively.

Thus, detection of DUSP22, TP63 gene rearrangements has great practical value in ALK-negative ALTCL. Statistical significance should be confirmed by further study.