@article{N Guillaume_C Alleaume_D Munfus_JC Capiod_G Touati_B Pautard_B Desablens_JJ Lefrere_F Gouilleux_K Lassoued_V Gouilleux-Gruart_2005, place={Pavia, Italy}, title={ZAP-70 tyrosine kinase is constitutively expressed and phosphorylated in B-lineage acute lymphoblastic leukemia cells}, volume={90}, url={https://haematologica.org/article/view/3587}, DOI={10.3324/%x}, abstractNote={BACKGROUND AND OBJECTIVES: Zeta-associated protein 70 (ZAP-70), a member of the Syk family of protein tyrosine kinases, is normally expressed in T and NK cells. While little is known about ZAP-70 expression in normal human B cells, it has been reported that ZAP-70 is expressed in a subset of patients with chronic lymphocytic leukemia (CLL) with a poor prognosis. In this study, we examined the expression and phosphorylation status of ZAP-70 in B-lineage acute lymphoblastic leukemia (Blin-ALL). DESIGN AND METHODS: First, ZAP-70 protein expression was assessed by Western blotting and flow cytometry and ZAP-70 mRNA transcripts were analyzed by reverse transcription polymerase chain reaction (RT-PCR) on human precursor B cell lines. Experiments were then carried out on cells obtained from 18 patients with Blin-ALL and from normal human bone marrow. RESULTS: ZAP-70 was constitutively expressed and phosphorylated on tyr319 in human precursor Blin-ALL cell lines as well as in primary B leukemic cells from all examined Blin-ALL patients with pro-B, pre-B and B phenotypes, but not in malignant myeloid cells. Importantly, analysis of normal human bone marrow revealed expression of ZAP-70 transcripts only in the CD34+ cell fraction (either CD19-CD10- or CD19+CD10+) but not in the CD34- cell fraction (CD19+sIgM- pre-B cells or CD19+sIgM+ immature B cells). INTERPRETATION AND CONCLUSIONS: ZAP-70 was found to be expressed in the CD34+ normal bone marrow compartment including earlier B-cell progenitors, but not in CD34- pre-B and immature B cells. By contrast, ZAP-70 was consistently expressed and phosphorylated in Blin-ALL cells. Further studies are required to determine whether ZAP-70 may play a pathophysiological role in Blin-ALL.}, number={7}, journal={Haematologica}, author={N Guillaume and C Alleaume and D Munfus and JC Capiod and G Touati and B Pautard and B Desablens and JJ Lefrere and F Gouilleux and K Lassoued and V Gouilleux-Gruart}, year={2005}, month={Jul.}, pages={899-905} }