ZAP-70 expression in acute lymphoblastic leukemia: association with the E2A/PBX1 rearrangement and the pre-B stage of differentiation and prognostic implications

Author:

Chiaretti Sabina1,Guarini Anna1,De Propris Maria Stefania1,Tavolaro Simona1,Intoppa Stefania1,Vitale Antonella1,Iacobelli Simona1,Elia Loredana1,Ariola Cristina1,Ritz Jerome1,Foà Robin1

Affiliation:

1. From the Division of Hematology, Department of Cellular Biotechnologies and Hematology, University “La Sapienza,” Rome, Italy; and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.

Abstract

AbstractWe evaluated the expression of 2 members of the Syk family, ZAP-70 and Syk, in acute lymphoblastic leukemia (ALL) samples, using data derived from a series of 33 T-ALL and 95 B-lineage adult ALL patients analyzed by oligonucleotide arrays. Of the B-lineage ALL cases, 37 were BCR/ABL+, 10 were ALL1/AF4+, 5 were E2A/PBX1+, and 43 carried no known molecular abnormality. ZAP-70 was highly expressed in T-ALL. A high ZAP-70 expression was also found in a proportion of B-lineage ALL, the highest levels being associated with the E2A/PBX1+ group and the lowest with ALL1/AF4+ cases (P < .001). A higher ZAP-70 expression was also observed in the pre-B group (P < .001). Remarkably, Syk expression was always preserved, suggesting that ZAP-70 expression is not substitutive of Syk. At the protein level, ZAP-70 was evaluated on 39 newly diagnosed ALL patients (25 adults, 14 children) and was detected in 23 cases (59%). ZAP-70 expression was consistently found in Igμ+ cases. Evaluation of long-term outcome in cases without molecular abnormalities showed that the higher levels of ZAP-70 were coupled to a higher relapse rate. In ALL, ZAP-70 expression is associated with the E2A/PBX1 rearrangement and pre-B stage and may have a prognostic role and be a candidate molecule for targeted therapies.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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