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

Abstract

We 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 Ig mu+ 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.

• Authors: Sabina Chiaretti, Anna Guarini, Maria Stefania De Propris, Simona Tavolaro, Stefania Intoppa, Antonella Vitale, Simona Iacobelli, Loredana Elia, Cristina Ariola, Jerome Ritz, Robin Foà
• Journal: Blood (Blood) Vol. 107 Issue 1 Pg. 197-204 (Jan 01 2006) ISSN: 0006-4971 [Print] United States
• PMID: 16160012 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Precursors
• Homeodomain Proteins
• Immunoglobulin mu-Chains
• Intracellular Signaling Peptides and Proteins
• Oncogene Proteins, Fusion
• E2A-Pbx1 fusion protein
• Protein-Tyrosine Kinases
• SYK protein, human
• Syk Kinase
• ZAP-70 Protein-Tyrosine Kinase

Topics

• Adult
• Cell Differentiation
• Child
• Enzyme Precursors (genetics)
• Follow-Up Studies
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Gene Rearrangement
• Homeodomain Proteins (genetics)
• Humans
• Immunoglobulin mu-Chains
• Intracellular Signaling Peptides and Proteins
• Oncogene Proteins, Fusion (genetics)
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (pathology)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics, pathology)
• Prognosis
• Protein-Tyrosine Kinases (genetics)
• Recurrence
• Syk Kinase
• ZAP-70 Protein-Tyrosine Kinase (genetics)