This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Teofili, L. Articles by Larocca, L. M. Search for Related Content PubMed PubMed Citation Articles by Teofili, L. Articles by Larocca, L. M. Social Bookmarking                            What's this?

Markers of Myeloproliferative Diseases in Childhood Polycythemia Vera and Essential Thrombocythemia

Luciana Teofili, Fiorina Giona, Maurizio Martini, Tonia Cenci, Francesco Guidi, Lorenza Torti, Giovanna Palumbo, Angela Amendola, Robin Foà, Luigi M. Larocca

From the Departments of Hematology and Pathology, Catholic University; Division of Hematology, Department of Cellular Biotechnologies and Hematology, La Sapienza University, Rome, Italy

Address reprint requests to Luigi M. Larocca, MD, Department of Pathology, Catholic University, Largo F. Vito 1, I-00168 Rome, Italy; e-mail: llarocca{at}rm.unicatt.it

Purpose Polycythemia vera (PV) and essential thrombocythemia (ET) can present in pediatric age as sporadic or familial diseases. To define the biologic profile of childhood PV and ET, we evaluated specific markers in a cohort of pediatric patients affected by PV and ET, including cases with familial occurrence.

Patients and Methods Thirty-eight children with PV and ET were investigated. The control group included 58 adults with PV and ET. Endogenous erythroid colonies, qualitative reverse transcriptase polymerase chain reaction for polycythemia rubra vera-1 (PRV-1) RNA expression, human androgen receptor assay and allele specific polymerase chain reaction for JAK2 V617F mutation were undertaken in all patients. Thrombopoietin, thrombopoietin receptor (c-mpl), and erythropoietin receptor mutation analysis was performed by direct sequencing in familial cases.

Results The JAK2 V617F mutation in children with PV was significantly less frequent than in adult PV. The most common myeloproliferative marker found in these patients was PRV-1 RNA overexpression. Children and adults with sporadic ET showed a similar proportion of patients with PRV-1 RNA overexpression, JAK2 V617F mutation, and clonality, while none of the familial ET showed JAK2 V617F mutation and clonality. Also, PRV-1 RNA overexpression was significantly less common. Furthermore, most patients with familial ET exhibited the dominant-positive activating mutation of c-mpl. Finally, children with PV and ET had a significant lower incidence of thrombosis than adults.

Conclusion This study demonstrates that familial and sporadic ET recognize different pathogenetic mechanisms. Myeloproliferative markers are specific tests for the diagnosis of ET in children with sporadic forms, while a significant proportion of children with PV can prove negative.

Supported in part by Fondi d’Ateneo, Progetti D1 2005 to 2006, Catholic University, Rome, Italy.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				K. Liu, M. Martini, B. Rocca, C. I. Amos, L. Teofili, F. Giona, J. Ding, H. Komatsu, L. M. Larocca, and R. C. Skoda Evidence for a founder effect of the MPL-S505N mutation in eight Italian pedigrees with hereditary thrombocythemia Haematologica, October 1, 2009; 94(10): 1368 - 1374. [Abstract] [Full Text] [PDF]

				C. Graziano, S. Carone, E. Panza, F. Marino, P. Magini, G. Romeo, A. Pession, and M. Seri Association of hereditary thrombocythemia and distal limb defects with a thrombopoietin gene mutation Blood, August 20, 2009; 114(8): 1655 - 1657. [Abstract] [Full Text] [PDF]

				R. Tiedt, J. Coers, S. Ziegler, A. Wiestner, H. Hao-Shen, C. Bornmann, J. Schenkel, S. Karakhanova, F. J. de Sauvage, C. W. Jackson, et al. Pronounced thrombocytosis in transgenic mice expressing reduced levels of Mpl in platelets and terminally differentiated megakaryocytes Blood, February 19, 2009; 113(8): 1768 - 1777. [Abstract] [Full Text] [PDF]

				M. Martini, L. Teofili, T. Cenci, F. Giona, L. Torti, M. Rea, R. Foa, G. Leone, and L. M. Larocca A novel heterozygous HIF2AM535I mutation reinforces the role of oxygen sensing pathway disturbances in the pathogenesis of familial erythrocytosis Haematologica, July 1, 2008; 93(7): 1068 - 1071. [Abstract] [Full Text] [PDF]

				P. A. Beer, P. J. Campbell, L. M. Scott, A. J. Bench, W. N. Erber, D. Bareford, B. S. Wilkins, J. T. Reilly, H. C. Hasselbalch, R. Bowman, et al. MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort Blood, July 1, 2008; 112(1): 141 - 149. [Abstract] [Full Text] [PDF]

				M. Cazzola Molecular basis of thrombocytosis Haematologica, May 1, 2008; 93(5): 646 - 648. [Full Text] [PDF]

				L. Teofili, R. Foa, F. Giona, and L. M. Larocca Childhood polycythemia vera and essential thrombocythemia: does their pathogenesis overlap with that of adult patients? Haematologica, February 1, 2008; 93(2): 169 - 172. [Full Text] [PDF]

				L. Teofili, F. Giona, M. Martini, T. Cenci, F. Guidi, L. Torti, G. Palumbo, A. Amendola, G. Leone, R. Foa, et al. The revised WHO diagnostic criteria for Ph-negative myeloproliferative diseases are not appropriate for the diagnostic screening of childhood polycythemia vera and essential thrombocythemia Blood, November 1, 2007; 110(9): 3384 - 3386. [Abstract] [Full Text] [PDF]

				L. Teofili, M. Martini, T. Cenci, G. Petrucci, L. Torti, S. Storti, F. Guidi, G. Leone, and L. M. Larocca Different STAT-3 and STAT-5 phosphorylation discriminates among Ph-negative chronic myeloproliferative diseases and is independent of the V617F JAK-2 mutation Blood, July 1, 2007; 110(1): 354 - 359. [Abstract] [Full Text] [PDF]

				R. Skoda The Genetic Basis of Myeloproliferative Disorders Hematology, January 1, 2007; 2007(1): 1 - 10. [Abstract] [Full Text] [PDF]

				A. M. Vannucchi and T. Barbui Thrombocytosis and Thrombosis Hematology, January 1, 2007; 2007(1): 363 - 370. [Abstract] [Full Text] [PDF]