Presence of the P2RY8-CRLF2 rearrangement is associated with a poor prognosis in non-high-risk precursor B-cell acute lymphoblastic leukemia in children treated according to the ALL-BFM 2000 protocol

被引：167

作者：

Cario, Gunnar ^{[1
]}

Zimmermann, Martin ^{[2
]}

Romey, Renja ^{[1
]}

Gesk, Stefan ^{[3
]}

Vater, Inga ^{[3
]}

Harbott, Jochen ^{[4
]}

Schrauder, Andre ^{[1
]}

Moericke, Anja ^{[1
]}

Izraeli, Shai ^{[5
,6
]}

Akasaka, Takashi ^{[7
]}

Dyer, Martin J. S. ^{[7
]}

Siebert, Reiner ^{[3
]}

Schrappe, Martin ^{[1
]}

Stanulla, Martin ^{[1
]}

机构：

[1] Univ Med Ctr Schleswig Holstein, Dept Pediat, D-24105 Kiel, Germany

[2] Hannover Med Sch, Dept Pediat Hematol & Oncol, Hannover, Germany

[3] Univ Kiel, Inst Human Genet, Kiel, Germany

[4] Univ Giessen, Dept Pediat Hematol & Oncol, Giessen, Germany

[5] Chaim Sheba Med Ctr, Canc Res Ctr, Ramat Gan, Israel

[6] Tel Aviv Univ, Sch Med, IL-69978 Tel Aviv, Israel

[7] Univ Leicester, MRC, Toxicol Unit, Leicester, Leics, England

来源：

BLOOD | 2010年 / 115卷 / 26期

关键词：

MINIMAL RESIDUAL DISEASE; TREATMENT RESPONSE; RECEPTOR GENE; AIEOP-BFM; CHILDHOOD; EXPRESSION; CRLF2; THERAPY;

D O I：

10.1182/blood-2009-11-256131

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

High-level expression of the cytokine receptor-like factor 2 gene, CRLF2, in precursor B-cell acute lymphoblastic leukemia (pB-ALL) was shown to be caused by a translocation involving the IGH@ locus or a deletion juxtaposing CRLF2 with the P2RY8 promoter. To assess its possible prognostic value, CRLF2 expression was analyzed in 555 childhood pB-ALL patients treated according to the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Munster 2000 (ALL-BFM 2000) protocol. Besides CRLF2 rearrangements, high-level CRLF2 expression was seen in cases with supernumerary copies of the CRLF2 locus. On the basis of the detection of CRLF2 rearrangements, a CRLF2 high-expression group (n = 49) was defined. This group had a 6-year relapse incidence of 31% plus or minus 8% compared with 11% plus or minus 1% in the CRLF2 low-expression group (P = .006). This difference was mainly attributable to an extremely high incidence of relapse (71% +/- 19%) in non-high-risk patients with P2RY8-CRLF2 rearrangement. The assessment of CRLF2 aberrations may therefore serve as new stratification tool in Berlin-Frankfurt-Munster-based protocols by identifying additional high-risk patients who may benefit from an intensified and/or targeted treatment. (Blood. 2010; 115(26):5393-5397)

引用

页码：5393 / 5397

页数：5

共 20 条

[1] Distinct gene expression profiles determine molecular treatment response in childhood acute lymphoblastic leukemia [J].

Cario, G ;

Stanulla, M ;

Fine, BM ;

Teuffel, O ;

Neuhoff, NV ;

Schrauder, A ;

Flohr, T ;

Schaier, BW ;

Bartram, CR ;

Welte, K ;

Schlegelberger, B ;

Schrappe, M .

BLOOD, 2005, 105 (02) :821-826

[2] High interleukin-15 expression characterizes childhood acute lymphoblastic leukemia with involvement of the CNS [J].

Cario, Gunnar ;

Izraeli, Shai ;

Teichert, Anja ;

Rhein, Peter ;

Skokowa, Julia ;

Moericke, Anja ;

Zimmermann, Martin ;

Schrauder, Andre ;

Karawajew, Leonid ;

Ludwig, Wolf-Dieter ;

Welte, Karl ;

Schuenemann, Holger J. ;

Schlegelberger, Brigitte ;

Schrappe, Martin ;

Stanulla, Martin .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (30) :4813-4820

[3] Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study [J].

Conter, Valentino ;

Bartram, Claus R. ;

Valsecchi, Maria Grazia ;

Schrauder, Andre ;

Panzer-Gruemayer, Renate ;

Moericke, Anja ;

Arico, Maurizio ;

Zimmermann, Martin ;

Mann, Georg ;

De Rossi, Giulio ;

Stanulla, Martin ;

Locatelli, Franco ;

Basso, Giuseppe ;

Niggli, Felix ;

Barisone, Elena ;

Henze, Guenter ;

Ludwig, Wolf-Dieter ;

Haas, Oskar A. ;

Cazzaniga, Giovanni ;

Koehler, Rolf ;

Silvestri, Daniela ;

Bradtke, Jutta ;

Parasole, Rosanna ;

Beier, Rita ;

van Dongen, Jacques J. M. ;

Biondi, Andrea ;

Schrappe, Martin .

BLOOD, 2010, 115 (16) :3206-3214

[4]

COX DR, 1972, J R STAT SOC B, V34, P187

[5] Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia [J].

Flohr, T. ;

Schrauder, A. ;

Cazzaniga, G. ;

Panzer-Gruemayer, R. ;

van der Velden, V. ;

Fischer, S. ;

Stanulla, M. ;

Basso, G. ;

Niggli, F. K. ;

Schaefer, B. W. ;

Sutton, R. ;

Koehler, R. ;

Zimmermann, M. ;

Valsecchi, M. G. ;

Gadner, H. ;

Masera, G. ;

Schrappe, M. ;

van Dongen, J. J. M. ;

Biondi, A. ;

Bartram, C. R. .

LEUKEMIA, 2008, 22 (04) :771-782

[6] A CLASS OF K-SAMPLE TESTS FOR COMPARING THE CUMULATIVE INCIDENCE OF A COMPETING RISK [J].

GRAY, RJ .

ANNALS OF STATISTICS, 1988, 16 (03) :1141-1154

[7] Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia [J].

Harvey, Richard C. ;

Mullighan, Charles G. ;

Chen, I-Ming ;

Wharton, Walker ;

Mikhail, Fady M. ;

Carroll, Andrew J. ;

Kang, Huining ;

Liu, Wei ;

Dobbin, Kevin K. ;

Smith, Malcolm A. ;

Carroll, William L. ;

Devidas, Meenakshi ;

Bowman, W. Paul ;

Camitta, Bruce M. ;

Reaman, Gregory H. ;

Hunger, Stephen P. ;

Downing, James R. ;

Willman, Cheryl L. .

BLOOD, 2010, 115 (26) :5312-5321

[8] Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group [J].

Hertzberg, Libi ;

Vendramini, Elena ;

Ganmore, Ithamar ;

Cazzaniga, Gianni ;

Schmitz, Maike ;

Chalker, Jane ;

Shiloh, Ruth ;

Iacobucci, Ilaria ;

Shochat, Chen ;

Zeligson, Sharon ;

Cario, Gunnar ;

Stanulla, Martin ;

Strehl, Sabine ;

Russell, Lisa J. ;

Harrison, Christine J. ;

Bornhauser, Beat ;

Yoda, Akinori ;

Rechavi, Gideon ;

Bercovich, Dani ;

Borkhardt, Arndt ;

Kempski, Helena ;

Kronnie, Geertruy Te ;

Bourquin, Jean-Pierre ;

Domany, Eytan ;

Izraeli, Shai .

BLOOD, 2010, 115 (05) :1006-1017

[9]

Kalbfleisch J.D., 1980, The Statistical Analysis of Failure Time Data, P163

[10] NONPARAMETRIC-ESTIMATION FROM INCOMPLETE OBSERVATIONS [J].

KAPLAN, EL ;

MEIER, P .

JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1958, 53 (282) :457-481

← 1 2 →