title: The expression pattern of c-mpl in megakaryocytes correlates with thrombotic risk in essential thrombocythemia.
abstract: Using immunohistochemistry, we investigated the expression of c-mpl in bone marrow megakaryocytes of 88 patients with essential thrombocythemia (ET), 6 patients with secondary thrombocytosis (ST), and 20 patients with lymphoma (controls). Considering both the pattern of expression and the staining intensity, we identified a uniform and a heterogeneous pattern of c-mpl expression. The uniform pattern was found in all the controls, all the patients with ST, and 28 of the patients with ET, with a strong staining intensity observed in most megakaryocytes (> 80%). In contrast, c-mpl expression was heterogeneous in 60 patients with ET, 18 of whom (30%) presented with thrombosis at diagnosis, a significant difference from patients with a uniform c-mpl pattern (2 of 28; 7%; P =.026). In particular, the overrepresentation of thrombotic complications in patients with a heterogeneous c-mpl expression pattern was found mainly among patients with a significant percentage (10% to 40%) of weakly stained or c-mpl-negative megakaryocytes (heterogeneous-weak pattern; 13 of 30; 43%; P =.002). Accordingly, this pattern was associated with a 6.1-fold increased risk of thrombosis compared with that of patients with a uniform c-mpl pattern. In conclusion, the presence of a heterogeneous pattern of c-mpl distribution in bone marrow megakaryocytes could be a useful diagnostic criterion in the differential diagnosis of thrombocytosis. Furthermore, detection of a significant percentage of weakly stained or c-mpl-negative megakaryocytes can identify patients with a higher risk of thrombosis.
authors.affiliation: Department of Hematology, Catholic University, Rome, Italy. lteofili@rm.unicatt.it
authors.forename: Luciana
authors.initials: L
authors.lastname: Teofili
authors.forename: Francesco
authors.initials: F
authors.lastname: Pierconti
authors.forename: Annalaura
authors.initials: A
authors.lastname: Di Febo
authors.forename: Nicola
authors.initials: N
authors.lastname: Maggiano
authors.forename: Nicola
authors.initials: N
authors.lastname: Vianelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Ascani
authors.forename: Elena
authors.initials: E
authors.lastname: Rossi
authors.forename: Stefano
authors.initials: S
authors.lastname: Pileri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Leone
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Larocca
authors.forename: Valerio
authors.initials: V
authors.lastname: De Stefano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008533:Megakaryocytes / Q000737:chemistry* / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism*; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D012189:Retrospective Studies; D012307:Risk Factors; D013920:Thrombocythemia, Essential / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D013927:Thrombosis / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human