PMID- 31221512
OWN - NLM
STAT- MEDLINE
DCOM- 20200806
LR  - 20200806
IS  - 2152-2669 (Electronic)
IS  - 2152-2669 (Linking)
VI  - 19
IP  - 8
DP  - 2019 Aug
TI  - Characteristics of Waldenstrom Macroglobulinemia in Korean Patients According to 
      Mutational Status of MYD88 and CXCR4: Analysis Using Ultra-Deep Sequencing.
PG  - e496-e505
LID - S2152-2650(18)31260-6 [pii]
LID - 10.1016/j.clml.2019.03.009 [doi]
AB  - BACKGROUND: Little is known about the mutational frequency of myeloid 
      differentiation factor 88 (MYD88) and C-X-C chemokine receptor type 4 (CXCR4) and 
      the corresponding characteristics in Asian individuals afflicted with Waldenstrom 
      macroglobulinemia (WM). We investigated the characteristics of WM according to 
      mutational status of MYD88/CXCR4, and attempted to determine the lineage 
      commitment among hematopoietic cells by MYD88(L265P) single-cell sequencing on 
      bone marrow (BM) smear slides. MATERIALS AND METHODS: CXCR4 mutations (muts) were 
      detected using ultra-deep sequencing using target capture. Mutational burden of 
      MYD88 was assessed using real-time polymerase chain reaction. Single-cell 
      sequencing for MYD88 was performed on lymphocytes, plasmacytoid lymphocytes, 
      plasma cells, and neutrophils using laser microdissection. RESULTS: Among 31 
      patients, the frequencies of MYD88/CXCR4 muts were as follows: MYD88 wild type 
      (WT) CXCR4(WT) (6 patients, 19.4%), MYD88(L265P)CXCR4(WT) (19 patients, 61.4%), 
      MYD88(L265P)CXCR4(mut) (6 patients, 19.4%; 1 frameshift and 5 nonsense muts). 
      Immunoglobulin M levels of MYD88(L265)CXCR4(WT) patients were significantly 
      higher than those of MYD88(WT)CXCR4(WT) patients (P = .024). Tumor burden in BM 
      was highest in patients with MYD88(L265P)CXCR4(mut) (82.0%), followed by 
      MYD88(L265P)CXCR4(WT) (52.8%) and MYD88(WT)CXCR4(WT) (14.2%) (P < .001). The 
      quantity of MYD88-mutated DNA tended to correlate with tumor burden in BM 
      (correlation coefficient 0.647; P = .009). MYD88(L265P) was detected in plasma 
      cells, plasmacytoid lymphocytes, and lymphocytes but not neutrophils. CONCLUSION: 
      The frequency of MYD88/CXCR4 muts in Korean and Caucasian patients with WM was 
      similar, however 5 of the 6 CXCR4 muts were nonsense-a proportion higher than 
      reported frequencies in Caucasian individuals. Ultra-deep sequencing was capable 
      of detecting CXCR4 muts not detectable using Sanger sequencing, suggesting a 
      possible replacement of the B-cell sorting.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Shin, Dong Woo
AU  - Shin DW
AD  - Department of Laboratory Medicine, Seoul National University College of Medicine, 
      Seoul, Korea.
FAU - Kim, Sung-Min
AU  - Kim SM
AD  - Cancer Research Institute, Seoul National University College of Medicine, Seoul, 
      Korea.
FAU - Kim, Jung-Ah
AU  - Kim JA
AD  - Department of Laboratory Medicine, Chung-Ang University Hospital, Seoul, Korea.
FAU - Park, Hee Sue
AU  - Park HS
AD  - Department of Laboratory Medicine, Seoul National University College of Medicine, 
      Seoul, Korea.
FAU - Hwang, Sang Mee
AU  - Hwang SM
AD  - Department of Laboratory Medicine, Seoul National University College of Medicine, 
      Seoul, Korea; Department of Laboratory Medicine, Seoul National University 
      Bundang Hospital, Seongnam, Korea.
FAU - Im, Kyongok
AU  - Im K
AD  - Cancer Research Institute, Seoul National University College of Medicine, Seoul, 
      Korea.
FAU - Kim, Sungsik
AU  - Kim S
AD  - Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, 
      Korea.
FAU - Kim, Jinhyun
AU  - Kim J
AD  - Department of Electrical and Computer Engineering, Seoul National University, 
      Seoul, Korea.
FAU - Kwon, Sunghoon
AU  - Kwon S
AD  - Department of Electrical and Computer Engineering, Seoul National University, 
      Seoul, Korea.
FAU - Yoon, Sung-Soo
AU  - Yoon SS
AD  - Cancer Research Institute, Seoul National University College of Medicine, Seoul, 
      Korea; Division of Hematology/Oncology, Department of Internal Medicine, Seoul 
      National University College of Medicine, Seoul, Korea.
FAU - Lee, Dong Soon
AU  - Lee DS
AD  - Department of Laboratory Medicine, Seoul National University College of Medicine, 
      Seoul, Korea; Cancer Research Institute, Seoul National University College of 
      Medicine, Seoul, Korea. Electronic address: soonlee@snu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190315
PL  - United States
TA  - Clin Lymphoma Myeloma Leuk
JT  - Clinical lymphoma, myeloma & leukemia
JID - 101525386
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Receptors, CXCR4)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*genetics
MH  - Cohort Studies
MH  - Female
MH  - Follow-Up Studies
MH  - High-Throughput Nucleotide Sequencing/*methods
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Myeloid Differentiation Factor 88/*genetics
MH  - Prognosis
MH  - Receptors, CXCR4/*genetics
MH  - Republic of Korea/epidemiology
MH  - Single-Cell Analysis
MH  - Waldenstrom Macroglobulinemia/epidemiology/*genetics/pathology
OTO - NOTNLM
OT  - CXCR4
OT  - MYD88
OT  - Single cell analysis
OT  - Ultra-deep sequencing
OT  - Waldenstrom macroglobulinemia
EDAT- 2019/06/22 06:00
MHDA- 2020/08/07 06:00
CRDT- 2019/06/22 06:00
PHST- 2018/08/14 00:00 [received]
PHST- 2019/01/21 00:00 [revised]
PHST- 2019/03/08 00:00 [accepted]
PHST- 2019/06/22 06:00 [pubmed]
PHST- 2020/08/07 06:00 [medline]
PHST- 2019/06/22 06:00 [entrez]
AID - S2152-2650(18)31260-6 [pii]
AID - 10.1016/j.clml.2019.03.009 [doi]
PST - ppublish
SO  - Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):e496-e505. doi: 
      10.1016/j.clml.2019.03.009. Epub 2019 Mar 15.