ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes.

Abstract:

:Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALK-positive ALCL but lacks chromosomal rearrangements of the ALK gene. The genetic and clinical heterogeneity of ALK-negative ALCL has not been delineated. We performed immunohistochemistry and fluorescence in situ hybridization on 73 ALK-negative ALCLs and 32 ALK-positive ALCLs and evaluated the associations among pathology, genetics, and clinical outcome. Chromosomal rearrangements of DUSP22 and TP63 were identified in 30% and 8% of ALK-negative ALCLs, respectively. These rearrangements were mutually exclusive and were absent in ALK-positive ALCLs. Five-year overall survival rates were 85% for ALK-positive ALCLs, 90% for DUSP22-rearranged ALCLs, 17% for TP63-rearranged ALCLs, and 42% for cases lacking all 3 genetic markers (P < .0001). Hazard ratios for death in these 4 groups after adjusting for International Prognostic Index and age were 1.0 (reference group), 0.58, 8.63, and 4.16, respectively (P = 7.10 × 10(-5)). These results were similar when restricted to patients receiving anthracycline-based chemotherapy, as well as to patients not receiving stem cell transplantation. Thus, ALK-negative ALCL is a genetically heterogeneous disease with widely disparate outcomes following standard therapy. DUSP22 and TP63 rearrangements may serve as predictive biomarkers to help guide patient management.

journal_name

Blood

journal_title

Blood

authors

Parrilla Castellar ER,Jaffe ES,Said JW,Swerdlow SH,Ketterling RP,Knudson RA,Sidhu JS,Hsi ED,Karikehalli S,Jiang L,Vasmatzis G,Gibson SE,Ondrejka S,Nicolae A,Grogg KL,Allmer C,Ristow KM,Wilson WH,Macon WR,Law ME,Ce

doi

10.1182/blood-2014-04-571091

subject

Has Abstract

pub_date

2014-08-28 00:00:00

pages

1473-80

issue

9

eissn

0006-4971

issn

1528-0020

pii

blood-2014-04-571091

journal_volume

124

pub_type

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