PMID- 33194739
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220418
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 10
DP  - 2020
TI  - Multi-Lineage BCR-ABL Expression in Philadelphia Chromosome-Positive Acute 
      Lymphoblastic Leukemia Is Associated With Improved Prognosis but No Specific 
      Molecular Features.
PG  - 586567
LID - 10.3389/fonc.2020.586567 [doi]
LID - 586567
AB  - BACKGROUND: Recently, various blood cell lineages expressing the BCR-ABL fusion 
      gene in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) 
      have been reported. However, the biological and clinical significance of these 
      BCR-ABL lineages has not been established; therefore, we aimed to clarify the 
      impacts of these different BCR-ABL-expressing lineages. PATIENTS: Multi-lineage 
      BCR-ABL expression (multi-Ph) was defined as BCR-ABL expression outside of the 
      B-lineage compartment, as determined by fluorescence in situ hybridization (FISH) 
      in peripheral blood neutrophils and bone marrow clots, and flow cytometry-sorted 
      polymerase chain reaction (PCR). We analyzed IKZF1 deletion patterns by PCR, 
      examined gene expression profiles using RNA sequencing, and compared treatment 
      outcomes across different BCR-ABL-expressing lineages. RESULTS: Among the 21 
      multi-Ph patients in our 59-patient cohort (36%), BCR-ABL expression was detected 
      at the multipotential progenitor level. However, no IKZF1 deletion patterns or 
      gene expression profiles were identified that were specific for multi-Ph. 
      However, multi-Ph patients were found to have better survival rates than patients 
      with uni-lineage BCR-ABL expression [event-free survival (EFS): 74 vs. 33%, P = 
      0.01; overall survival (OS): 79 vs. 44% at 4 years, P = 0.01]. In multivariate 
      analyses, multi-Ph was identified as a good prognostic factor for both EFS and 
      OS. CONCLUSION: We confirmed that more than one-third of Ph+ALL patients could be 
      classified as mutli-Ph. Although no specific molecular characteristics were 
      identified for multi-Ph, this phenotype was associated with better treatment 
      outcomes.
CI  - Copyright (c) 2020 Nishiwaki, Kim, Ito, Maeda, Okuno, Koyama, Ozawa, Gunji, Osaki, 
      Kitamura, Ushijima, Ishikawa, Miyamura, Sugiura and Kiyoi.
FAU - Nishiwaki, Satoshi
AU  - Nishiwaki S
AD  - Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan.
FAU - Kim, Jeong Hui
AU  - Kim JH
AD  - Department of Hematology and Oncology, Nagoya University Graduate School of 
      Medicine, Nagoya, Japan.
FAU - Ito, Masafumi
AU  - Ito M
AD  - Department of Pathology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, 
      Japan.
FAU - Maeda, Matsuyoshi
AU  - Maeda M
AD  - Division of Pathology, Toyohashi Municipal Hospital, Toyohashi, Japan.
FAU - Okuno, Yusuke
AU  - Okuno Y
AD  - Medical Genomics Center, Nagoya University Hospital, Nagoya, Japan.
FAU - Koyama, Daisuke
AU  - Koyama D
AD  - Division of Hematology and Oncology, Toyohashi Municipal Hospital, Toyohashi, 
      Japan.
FAU - Ozawa, Yukiyasu
AU  - Ozawa Y
AD  - Department of Hematology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, 
      Japan.
FAU - Gunji, Masaharu
AU  - Gunji M
AD  - Department of Pathology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, 
      Japan.
FAU - Osaki, Masahide
AU  - Osaki M
AD  - Department of Hematology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, 
      Japan.
FAU - Kitamura, Kunio
AU  - Kitamura K
AD  - Division of Hematology, Ichinomiya Municipal Hospital, Ichinomiya, Japan.
FAU - Ushijima, Yoko
AU  - Ushijima Y
AD  - Department of Hematology and Oncology, Nagoya University Graduate School of 
      Medicine, Nagoya, Japan.
FAU - Ishikawa, Yuichi
AU  - Ishikawa Y
AD  - Department of Hematology and Oncology, Nagoya University Graduate School of 
      Medicine, Nagoya, Japan.
FAU - Miyamura, Koichi
AU  - Miyamura K
AD  - Department of Hematology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, 
      Japan.
FAU - Sugiura, Isamu
AU  - Sugiura I
AD  - Division of Hematology and Oncology, Toyohashi Municipal Hospital, Toyohashi, 
      Japan.
FAU - Kiyoi, Hitoshi
AU  - Kiyoi H
AD  - Department of Hematology and Oncology, Nagoya University Graduate School of 
      Medicine, Nagoya, Japan.
LA  - eng
PT  - Journal Article
DEP - 20201023
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC7646258
OTO - NOTNLM
OT  - BCR-ABL-expressing lineage
OT  - Philadelphia chromosome-positive acute lymphoblastic leukemia
OT  - multi-lineage
OT  - multipotent progenitor
OT  - uni-lineage
EDAT- 2020/11/17 06:00
MHDA- 2020/11/17 06:01
PMCR- 2020/01/01
CRDT- 2020/11/16 08:52
PHST- 2020/07/23 00:00 [received]
PHST- 2020/09/30 00:00 [accepted]
PHST- 2020/11/16 08:52 [entrez]
PHST- 2020/11/17 06:00 [pubmed]
PHST- 2020/11/17 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2020.586567 [doi]
PST - epublish
SO  - Front Oncol. 2020 Oct 23;10:586567. doi: 10.3389/fonc.2020.586567. eCollection 
      2020.