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Leuk Res. 2016 Feb;41:36-42. doi: 10.1016/j.leukres.2015.11.018. Epub 2015 Dec 23.

CRLF2 overexpression identifies an unfavourable subgroup of adult B-cell precursor acute lymphoblastic leukemia lacking recurrent genetic abnormalities.

Author information

1
Hematology, Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Italy.
2
GIMEMA Data Center, Rome, Italy.
3
Division of Hematology, AOU Policlinico-OVE, University of Catania, Italy.
4
Division of Hematology and Stem Cell Transplantation Unit, Cardarelli Hospital, Naples, Italy.
5
Hematology, Sant'Eugenio Hospital, Rome, Italy.
6
Hematology Division, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
7
Hematology Unit, Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio Calabria, Italy.
8
Laboratory of Oncohematology, Department of Women's and Children's Health, University of Padova, Italy.
9
Hematology, Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Italy. Electronic address: rfoa@bce.uniroma1.it.

Abstract

BACKGROUND:

A deregulated CRLF2 (d-CRLF2) expression was described in B-cell acute lymphoblastic leukemia without recurrent fusion genes (B-NEG ALL). While the role of d-CRLF2 in children has been extensively described, little is known about its role and impact in adult ALL.

METHODS:

Expression levels of CRLF2 were evaluated by quantitative real-time PCR in 102 newly-diagnosed adult B-NEG ALL and correlated with the clinico-biological characteristics and outcome. Incidence and clinical impact of the P2RY8/CRLF2 transcript was also assessed.

RESULTS:

High CRLF2 levels, as continuous variable, were significantly associated with hyperleucocytosis (p=0.0002) and thrombocytopenia (p=0.005); when a cut-point at ΔCt≤8 was applied, 35 cases (34.3%), mostly males (80%), proved positive for CRLF2 expression. High CRLF2 levels, as continuous or categorical variable, were associated with a worse disease-free (p=0.003 and p=0.015) and overall survival (p=0.017 and 0.0038). Furthermore, when CRLF2 was analyzed as a categorical variable, a high statistical association was found with IKZF1 deletion and mutations in the JAK/STAT pathway (p=0.001 and p<0.0001, respectively). Finally, the P2RY8/CRLF2 transcript, identified in 8/102 patients (7.8%), was associated with a poor outcome.

CONCLUSIONS:

In adult B-NEG ALL, high CRLF2 expression is associated with distinct clinico-biological features and an unfavourable prognosis in both univariate and multivariate analysis; similarly, P2RY8/CRLF2 positivity correlates with a poor outcome. The quantification of CRLF2 is an important prognostic marker in adult B-lineage ALL without known genetic lesions.

KEYWORDS:

Acute lymphoblastic leukemia; Adult patients; CRLF2 overexpression; Prognosis

PMID:
26754556
DOI:
10.1016/j.leukres.2015.11.018
[Indexed for MEDLINE]

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