ZAP-70 expression in acute lymphoblastic leukemia: association with the E2A/PBX1 rearrangement and the pre-B stage of differentiation and prognostic implications.
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.
Chiaretti
Sabina
S
Division of Hematology, University La Sapienza, Via Benevento 6, 00161 Rome, Italy.
Guarini
Anna
A
De Propris
Maria Stefania
MS
Tavolaro
Simona
S
Intoppa
Stefania
S
Vitale
Antonella
A
Iacobelli
Simona
S
Elia
Loredana
L
Ariola
Cristina
C
Ritz
Jerome
J
Foà
Robin
R
D000328:Adult; D002454:Cell Differentiation; D002648:Child; D004792:Enzyme Precursors / Q000235:genetics; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007148:Immunoglobulin mu-Chains; D047908:Intracellular Signaling Peptides and Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D012008:Recurrence; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics*
D004792:Enzyme Precursors; D018398:Homeodomain Proteins; D007148:Immunoglobulin mu-Chains; D047908:Intracellular Signaling Peptides and Proteins; D015514:Oncogene Proteins, Fusion; C089847:E2A-Pbx1 fusion protein; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase