Poor prognosis for P2RY8-CRLF2 fusion but not for CRLF2 over-expression in children with intermediate risk B-cell precursor acute lymphoblastic leukemia

被引：100

作者：

Palmi, C. ^{[1
]}

Vendramini, E. ^{[2
]}

Silvestri, D. ^{[3
]}

Longinotti, G. ^{[1
]}

Frison, D. ^{[2
]}

Cario, G. ^{[4
]}

Shochat, C. ^{[5
,6
,7
]}

Stanulla, M. ^{[4
]}

Rossi, V. ^{[1
]}

Di Meglio, A. M. ^{[2
]}

Villa, T. ^{[1
]}

Giarin, E. ^{[2
]}

Fazio, G. ^{[1
]}

Leszl, A. ^{[2
]}

Schrappe, M. ^{[4
]}

Basso, G. ^{[2
]}

Biondi, A.

Izraeli, S. ^{[5
,6
]}

Conter, V. ^{[8
]}

Valsecchi, M. G. ^{[3
]}

Cazzaniga, G. ^{[1
]}

te Kronnie, G. ^{[2
]}

机构：

[1] Univ Milano Bicocca, Osped San Gerardo, Clin Pediat, Ctr Ric Tettamanti, I-20900 Monza, Italy

[2] Univ Padua, Dept Pediat, Lab Oncohematol, Padua, Italy

[3] Univ Milano Bicocca, Ctr Biostat Epidemiol Clin, I-20900 Monza, Italy

[4] Univ Hosp Schleswig Holstein, Dept Pediat, Kiel, Germany

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

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

[7] Migal Galilee Biotechnol Ctr, Kiryat Shmona, Israel

[8] Osped Riuniti Bergamo, I-24100 Bergamo, Italy

来源：

LEUKEMIA | 2012年 / 26卷 / 10期

基金：

以色列科学基金会;

关键词：

CRLF2; pediatric BCP-ALL; prognosis; REARRANGEMENT; CHILDHOOD; BFM; PROGENITOR; DELETION; DISEASE; IKZF1; GENE;

D O I：

10.1038/leu.2012.101

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has achieved an 80% cure rate as a result of a risk-adapted therapy largely based on minimal residual disease (MRD) monitoring. However, relapse is still the most frequent adverse event, occurring mainly in the patients with intermediate MRD levels (intermediate risk, IR), emphasizing the need for new prognostic markers. We analyzed the prognostic impact of cytokine receptor-like factor 2 (CRLF2) over-expression and P2RY8-CRLF2 fusion in 464 BCP-ALL patients (not affected by Down syndrome and BCR-ABL negative) enrolled in the AIEOP-BFM ALL2000 study in Italy. In 22/464 (4.7%) samples, RQ-PCR showed CRLF2 over-expression (>= 20 times higher than the overall median). P2RY8-CRLF2 fusion was detected in 22/365 (6%) cases, with 10/22 cases also showing CRLF2 over-expression. P2RY8-CRLF2 fusion was the most relevant prognostic factor independent of CRLF2 over-expression with a threefold increase in risk of relapse. Significantly, the cumulative incidence of relapse of the P2RY8-CRLF2+ patients in the IR group was high (61.1% +/- 12.9 vs 17.6% +/- 2.6, P < 0.0001), similar to high-risk patients in AIEOP-BFM ALL2000 study. These results were confirmed in a cohort of patients treated in Germany. In conclusion, P2RY8-CRLF2 identifies a subset of BCP-ALL patients currently stratified as IR that could be considered for treatment intensification.

引用

页码：2245 / 2253

页数：9

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