The Eutos Population-Based Registry : Evaluation of Baseline Characteristics and First Treatment Choices Of 2983 Newly Diagnosed Chronic Myeloid Leukemia (Cml) Patients from 20 European Countries

Introduction

Somatic frameshift mutations in exon 9 of the calreticulin (CALR) gene were recently identified in patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs), particularly essential thrombocythemia and myelofibrosis.1, 2 Calreticulin is a highly conserved endoplasmic reticulum (ER) luminal Ca2+-binding chaperone protein with a critical role in the process of glycoprotein folding and a number of other cellular functions both inside and outside the ER,3, 4 and has three domains with different structural and functional properties; a globular N domain, a proline-rich P domain and an acidic C domain.3, 4 The disrupted C-terminal region contains a KDEL ER-retention sequence multiple sites with high capacity for Ca2+ binding and sites for binding to the cell surface and to blood clotting factors.5, 6

Thirty hairy cell leukemia patients were evaluated repeatedly for their bone marrow (BM) histology. At the time of diagnosis, 18 (60%) had diffuse, 9 (30%) had interstitial, and 2 (10%) had a mixed (diffuse and interstitial) pattern of BM disease. The follow-up BM specimens were obtained at intervals of 3-24 months, and the follow-up observation period was 12-94 months. In patients who were nontreated or only splenectomized, no significant changes were observed except of a persistent megaloblastoid picture of the red cell series and an increase of BM fibrosis. In the alpha-interferon treated patients a complete disappearance of hairy cells was observed in one and a dramatic reduction in five. The hairy cell index was reduced from a mean of 0.8 before to 0.1 after alpha-interferon therapy; most patients displayed megaloblastoid erythropoiesis. In the complete responder features of myelodysplasia were present.