Title: Coexistence of <i>JAK2</i> and <i>CALR</i> mutations and their clinical implications in patients with essential thrombocythemia
Abstract: // Min-Gu Kang 1, 2, * , Hyun-Woo Choi 1, * , Jun Hyung Lee 1 , Yong Jun Choi 1 , Hyun-Jung Choi 1 , Jong-Hee Shin 1 , Soon-Pal Suh 1 , Michael Szardenings 4 , Hye-Ran Kim 5 , Myung-Geun Shin 1, 2, 3 1 Departments of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, South Korea 2 Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, South Korea 3 Environmental Health Center for Childhood Leukemia and Cancer, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun-eup, Hwasun-gun, Jeollanam-do, South Korea 4 Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany 5 College of Korean Medicine, Dongshin University, Naju, Jeollanam-do, South Korea * Min-Gu Kang and Hyun-Woo Choi contributed equally to this work Correspondence to: Hye-Ran Kim, email: [email protected] Myung-Geun Shin, email: [email protected] Keywords: calreticulin, coexistence, essential thrombocythemia, Janus kinase 2, myeloproliferative disorders Received: April 15, 2016 Accepted: July 19, 2016 Published: July 30, 2016 ABSTRACT Janus kinase 2 ( JAK2 ) and calreticulin ( CALR ) constitute the two most frequent mutations in essential thrombocythemia (ET), and both are reported to be mutually exclusive. Hence, we examined a cohort of 123 myeloproliferative neoplasm (MPN) patients without BCR-ABL1 rearrangement and additional ET patients (n=96) for coexistence of JAK2 and CALR mutations. The frequency of CALR mutations was 20.3% in 123 MPN patients; 31.1% in ET (n=74), 25% in primary myelofibrosis (n=4) and 2.2% in polycythemia vera (n=45). JAK2 and CALR mutations coexisted in 7 (4.2%) of 167 ET patients. Clinical characteristics, progression-free survival (PFS), and elapsed time to achieve partial remission across 4 groups ( JAK2+/CALR+, JAK2+/CALR-, JAK2-/CALR+, JAK2-/CALR- ) were reviewed. The JAK2+/CALR- group had higher leukocyte counts and hemoglobin levels and more frequent thrombotic events than JAK2-/CALR- group. JAK2 mutations have a greater effect on the disease phenotype and the clinical features of MPN patients rather than do CALR mutation. JAK2+ groups showed a tendency of poor PFS than JAK2 - groups regardless of CALR mutation. CALR+ was a predictor of late response to the treatment. Our study also showed that thrombosis was more frequent in ET patients with type 2 CALR mutations than in those with type 1 CALR mutations.