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

被引：352

作者：

Castellar, Edgardo R. Parrilla ^{[1
]}

Jaffe, Elaine S. ^{[2
]}

Said, Jonathan W. ^{[3
]}

Swerdlow, Steven H. ^{[4
]}

Ketterling, Rhett P. ^{[1
]}

Knudson, Ryan A. ^{[1
]}

Sidhu, Jagmohan S. ^{[5
]}

Hsi, Eric D. ^{[6
]}

Karikehalli, Shridevi ^{[7
]}

Jiang, Liuyan ^{[8
]}

Vasmatzis, George ^{[9
]}

Gibson, Sarah E. ^{[4
]}

Ondrejka, Sarah ^{[6
]}

Nicolae, Alina ^{[2
]}

Grogg, Karen L. ^{[1
]}

Allmer, Cristine ^{[10
]}

Ristow, Kay M. ^{[11
]}

Wilson, Wyndham H. ^{[12
]}

Macon, William R. ^{[1
]}

Law, Mark E. ^{[1
]}

Cerhan, James R. ^{[10
]}

Habermann, Thomas M. ^{[11
]}

Ansell, Stephen M. ^{[11
]}

Dogan, Ahmet ^{[1
]}

Maurer, Matthew J. ^{[10
]}

Feldman, Andrew L. ^{[1
]}

机构：

[1] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA

[2] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA

[4] Univ Pittsburgh, Med Ctr, Div Hematopathol, Pittsburgh, PA USA

[5] United Hlth Serv Hosp, Dept Pathol & Lab Med, Johnson City, NY USA

[6] Cleveland Clin, Dept Clin Pathol, Cleveland, OH 44106 USA

[7] Centrex Clin Labs, Dept Pathol & Lab Med, Utica, NY USA

[8] Mayo Clin, Dept Lab Med & Pathol, Jacksonville, FL 32224 USA

[9] Mayo Clin, Ctr Individualized Med, Rochester, MN 55905 USA

[10] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA

[11] Mayo Clin, Div Hematol, Rochester, MN 55905 USA

[12] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA

来源：

BLOOD | 2014年 / 124卷 / 09期

关键词：

PERIPHERAL T-CELL; TRANSLOCATIONS;

D O I：

10.1182/blood-2014-04-571091

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 x 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.

引用

页码：1473 / 1480

页数：8

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