ZAP-70 tyrosine kinase is constitutively expressed and phosphorylated in B-lineage acute lymphoblastic leukemia cells.

Nicolas Guillaume (1, 2) , Céline Alleaume (1, 2) , Délicia Munfus (3) , Jean-Claude Capiod (4) , Gilles Touati (4) , Brigitte Pautard (4) , Bernard Desablens (4) , Jean-Jacques Lefrere (2) , Fabrice Gouilleux (1, 2) , Kaiss Lassoued (1, 2) , Valérie Gouilleux-Gruart (1, 2)

1 INSERM - Institut National de la Santé et de la Recherche Médicale
2 Laboratoire d'Hématologie [CHU Amiens]
3 UAB - University of Alabama at Birmingham [ Birmingham]
4 CHU Amiens-Picardie

ACKGROUND 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..

Keywords: ZAP-70; SYK; acute lymphoblastic leukemia; precursor B cells; B-lymphocytes

Domains: Life Sciences [q-bio]; Cancer

Nicolas Guillaume, Céline Alleaume, Délicia Munfus, Jean-Claude Capiod, Gilles Touati, et al.. ZAP-70 tyrosine kinase is constitutively expressed and phosphorylated in B-lineage acute lymphoblastic leukemia cells.. Haematologica, 2005, 90 (7), pp.899-905. ⟨10.3324/%25x⟩. ⟨hal-02424615⟩