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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5473-5476.
Prepublished online as a Blood First Edition Paper on March 9, 2007; DOI 10.1182/blood-2006-05-021071.


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NEOPLASIA

Brief Report

ERK1/2 phosphorylation is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia

Chiara Gregorj1, Maria R. Ricciardi1, Maria T. Petrucci1, Maria C. Scerpa1, Fabiana De Cave1, Paola Fazi2, Marco Vignetti1, Antonella Vitale1, Marco Mancini1, Giuseppe Cimino1, Salvatore Palmieri3, Francesco Di Raimondo4, Giorgina Specchia5, Francesco Fabbiano6, Nicola Cantore7, Federico Mosna8, Andrea Camera9, Mario Luppi10, Luciana Annino11, Eustachio Miraglia12, Giuseppe Fioritoni13, Francesca Ronco14, Giovanna Meloni1, Franco Mandelli1, Michael Andreeff15, Michele Milella16, Robin Foà1, Agostino Tafuri, the GIMEMA Acute Leukemia Working Party, Italy1

1 Division of Hematology, Department of Cellular Biotechnologies and Hematology, University "La Sapienza" of Rome, Italy; 2 Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) Foundation, Data Center, Rome, Italy; 3 Divisione di Ematologia–Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli," Napoli, Italy; 4 Cattedra di Ematologia–Ospedale "Ferrarotto," Università degli Studi di Catania, Italy; 5 Unità Operativa Ematologia 1, Università degli Studi di Bari, Italy; 6 Divisione di Ematologia, Azienda Ospedaliera "V. Cervello" di Palermo, Italy; 7 Ematologia, Azienda Ospedaliera "S.G. Moscati" di Avellino, Italy; 8 Divisione di Ematologia, Policlinico G.B. Rossi, Università degli Studi di Verona, Italy; 9 Ematologia, Università degli Studi Federico II di Napoli, Italy; 10 Dipartimento di Oncologia ed Ematologia, Università degli Studi di Modena e Reggio Emilia, Italy; 11 Unità Operativa di Ematologia, Complesso Ospedaliero S. Giovanni Addolorata di Roma, Italy; 12 Divisione di Ematologia, A.S.L. Napoli 1 Ospedale San Giovanni Bosco di Napoli, Italy; 13 Unità Operativa di Ematologia Clinica, Azienda USL di Pescara, Italy; 14 Dipartimento Emato-Oncologia Azienda Ospedaliera "Bianchi-Melacrino-Morelli" di Reggio Calabria, Italy; 15 Section of Molecular Hematology and Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; 16 Division of Medical Oncology A, Regina Elena Cancer Institute, Rome, Italy

Extracellular signal-regulated kinase-1/2 (ERK1/2) is frequently found constitutively activated (p-ERK1/2) in hematopoietic diseases, suggesting a role in leukemogenesis. The aim of this study was to assess the expression and clinical role of p-ERK1/2 in adult acute lymphoblastic leukemia (ALL). In 131 primary samples from adult de novo ALL patients enrolled in the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) Leucemia Acute Linfoide (LAL) 2000 protocol and evaluated by flow cytometry, constitutive ERK1/2 activation was found in 34.5% of cases; these results were significantly associated with higher white blood cell (WBC) values (P = .013). In a multivariate analysis, p-ERK1/2 expression was an independent predictor of complete remission achievement (P = .027). Effective approaches toward MEK inhibition need to be explored in order to evaluate whether this may represent a new therapeutic strategy for adult ALL patients.


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