Increased B cell activation is present in JAK2V617F-mutated, CALR-mutated and triple-negative essential thrombocythemia
In: Oncotarget, Jg. 8 (2017-03-18), S. 32476-32491
Online
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Zugriff:
// Ken-Hong Lim 1,2,3,4 , Caleb Gon-Shen Chen 2,3,4,5 , Yu-Cheng Chang 2,3,4 , Yi-Hao Chiang 2,3 , Chen-Wei Kao 3 , Wei-Ting Wang 3 , Chiao-Yi Chang 3 , Ling Huang 3 , Ching-Sung Lin 3 , Chun-Chia Cheng 3 , Hung-I Cheng 6 , Nai-Wen Su 2,3,4 , Johnson Lin 2 , Yi-Fang Chang 2,3,4 , Ming-Chih Chang 2,3,4 , Ruey-Kuen Hsieh 2,3 , Huan-Chau Lin 2,3 and Yuan-Yeh Kuo 1 1 Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan 2 Department of Internal Medicine, Division of Hematology and Oncology, MacKay Memorial Hospital, Taipei, Taiwan 3 Department of Medical Research, Laboratory of Good Clinical Research Center, MacKay Memorial Hospital, Tamsui District, New Taipei City, Taiwan 4 Department of Medicine, MacKay Medical College, New Taipei City, Taiwan 5 Institute of Molecular and Cellular Biology, National Tsing-Hua University, Hsinchu, Taiwan 6 Department of Internal Medicine, Division of Hematology and Oncology, MacKay Memorial Hospital, Hsinchu, Taiwan Correspondence to: Ken-Hong Lim, email: // Huan-Chau Lin, email: // Yuan-Yeh Kuo, email: // Keywords : B cell, CALR, essential thrombocythemia, immune Received : January 06, 2017 Accepted : February 28, 2017 Published : March 18, 2017 Abstract Essential thrombocythemia (ET) is a BCL-ABL1 -negative myeloproliferative neoplasm. We have reported that increased activated B cells can facilitate platelet production mediated by cytokines regardless JAK2 mutational status in ET. Recently, calreticulin ( CALR ) mutations were discovered in ~30% JAK2 / MPL- unmutated ET and primary myelofibrosis. Here we sought to screen for CALR mutations and to evaluate B cell immune profiles in a cohort of adult Taiwanese ET patients. B cell populations, granulocytes/monocytes membrane-bound B cell-activating factor (mBAFF) levels, B cells toll-like receptor 4 (TLR4) expression and intracellular levels of interleukin (IL)-1β/IL-6 and the expression of CD69, CD80, and CD86 were quantified by flow cytometry. Serum BAFF concentration was measured by ELISA. 48 healthy adults were used for comparison. 19 (35.2%) of 54 ET patients harbored 8 types of CALR exon 9 mutations including 4 (7.4%) patients with concomitant JAK2 V617F mutations. Compared to JAK2 V617F mutation, CALR mutations correlated with younger age at diagnosis ( p =0.04), higher platelet count ( p =0.004), lower hemoglobin level ( p =0.013) and lower leukocyte count ( p =0.013). Multivariate analysis adjusted for age, sex, follow-up period and hematological parameters confirmed that increased activated B cells were universally present in JAK2 -mutated, CALR -mutated and triple-negative ET patients when compared to healthy adults. JAK2 - and CALR -mutated ET have significantly higher fraction of B cells with TLR4 expression when compared to triple-negative ET ( p =0.019 and 0.02, respectively). CALR -mutated ET had significantly higher number of CD69-positive activated B cells when compared to triple-negative ET ( p =0.035). In conclusion, increased B cell activation is present in ET patients across different mutational subgroups.
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Increased B cell activation is present in JAK2V617F-mutated, CALR-mutated and triple-negative essential thrombocythemia
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Autor/in / Beteiligte Person: | Chang, Ming-Chih ; Kuo, Yuan-Yeh ; Caleb Gon-Shen Chen ; Huang, Ling ; Wang, Wei-Ting ; Chang, Yu-Cheng ; Kao, Chen-Wei ; Hsieh, Ruey-Kuen ; Lin, Huan-Chau ; Su, Nai-Wen ; Chang, Yi-Fang ; Cheng, Hung-I ; Chiang, Yi-Hao ; Lin, Ching-Sung ; Cheng, Chun-Chia ; Lin, Johnson ; Chang, Chiao-Yi ; Lim, Ken-Hong |
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Zeitschrift: | Oncotarget, Jg. 8 (2017-03-18), S. 32476-32491 |
Veröffentlichung: | Impact Journals, LLC, 2017 |
Medientyp: | unknown |
ISSN: | 1949-2553 (print) |
DOI: | 10.18632/oncotarget.16381 |
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