PMID- 32238402
OWN - NLM
STAT- MEDLINE
DCOM- 20210527
LR  - 20210527
IS  - 2373-2873 (Electronic)
IS  - 2373-2873 (Linking)
VI  - 6
IP  - 2
DP  - 2020 Apr
TI  - The diagnostic challenges and clinical course of a myeloid/lymphoid neoplasm with 
      eosinophilia and ZBTB20-JAK2 gene fusion presenting as B-lymphoblastic leukemia.
LID - 10.1101/mcs.a004937 [doi]
LID - a004937
AB  - We report the diagnostic challenges and the clinical course of a patient with an 
      extraordinary presentation of B-lymphoblastic leukemia (B-ALL) with eosinophilia. 
      We identified a novel ZBTB20-JAK2 gene fusion as a chimeric RNA transcript using 
      the Archer platform. This gene fusion from the same patient was recently 
      identified by Peterson et al. (2019) at the genomic level using a different 
      sequencing technology platform. The configuration of this gene fusion predicts 
      the production of a kinase-activating JAK2 fusion protein, which would normally 
      lead to a diagnosis of Philadelphia chromosome-like B-ALL (Ph-like B-ALL). 
      However, the unusual presentation of eosinophilia led us to demonstrate the 
      presence of this gene fusion in nonlymphoid hematopoietic cells by fluorescence 
      in situ hybridization (FISH) studies with morphologic correlation. Therefore, we 
      believe this disease, in fact, represents blast crisis arising from an underlying 
      myeloid neoplasm with JAK2 rearrangements. This case illustrates the difficulty 
      in differentiating Ph-like B-ALL and myeloid/lymphoid neoplasm with eosinophilia 
      and gene rearrangements (MLN-EGR) in blast crisis. As currently defined, the 
      diagnosis of MLN-EGR relies on the hematologic presentations and the 
      identification of marker gene fusions (including PCM1-JAK2, ETV6-JAK2, and 
      BCR-JAK2). However, these same gene fusions, when limited to B-lymphoblasts, also 
      define Ph-like B-ALL. Yet, our case does not conform to either condition. 
      Therefore, the assessment for lineage restriction of gene rearrangements to 
      reflect the pathophysiologic difference between B-ALL and MLN-EGR in blast crisis 
      is likely a more robust diagnostic approach and allows the inclusion of MLN-EGR 
      with novel gene fusions.
CI  - (c) 2020 Lee et al.; Published by Cold Spring Harbor Laboratory Press.
FAU - Lee, Winston Y
AU  - Lee WY
AD  - Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, 
      Michigan 48109-2800, USA.
FAU - Pfau, Ruthann B
AU  - Pfau RB
AD  - Institute of Genomic Medicine, Nationwide Children's Hospital and Department of 
      Pathology, the Ohio State University, Columbus, Ohio 43205-2664, USA.
FAU - Choi, Sarah M
AU  - Choi SM
AD  - Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, 
      Michigan 48109-2800, USA.
FAU - Yang, Jiong
AU  - Yang J
AD  - Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, 
      Michigan 48109-2800, USA.
FAU - Xiao, Hong
AU  - Xiao H
AD  - Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, 
      Michigan 48109-2800, USA.
FAU - Putnam, Eileen M
AU  - Putnam EM
AD  - Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, 
      Michigan 48109-2800, USA.
FAU - Ryan, Russell Jh
AU  - Ryan RJ
AD  - Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, 
      Michigan 48109-2800, USA.
FAU - Bixby, Dale L
AU  - Bixby DL
AD  - Division of Hematology and Medical Oncology, Department of Internal Medicine, 
      Michigan Medicine, University of Michigan, Ann Arbor, Michigan 48109-2800, USA.
FAU - Shao, Lina
AU  - Shao L
AD  - Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, 
      Michigan 48109-2800, USA.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200401
PL  - United States
TA  - Cold Spring Harb Mol Case Stud
JT  - Cold Spring Harbor molecular case studies
JID - 101660017
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Transcription Factors)
RN  - 0 (ZBTB20 protein, human)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - Pdgfrb-Associated Chronic Eosinophilic Leukemia
SB  - IM
MH  - Adult
MH  - Biopsy
MH  - Bone Marrow/pathology
MH  - Combined Modality Therapy
MH  - Female
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Hypereosinophilic Syndrome/diagnosis/genetics
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Janus Kinase 2/*genetics
MH  - Karyotyping
MH  - Leukemia/*diagnosis/*genetics/therapy
MH  - Leukemia, Myelomonocytic, Chronic/diagnosis/genetics
MH  - Nerve Tissue Proteins/*genetics
MH  - Oncogene Proteins, Fusion/*genetics
MH  - *Phenotype
MH  - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/genetics
MH  - Therapeutics
MH  - Transcription Factors/*genetics
PMC - PMC7133749
OTO - NOTNLM
OT  - Ph-positive acute lymphoblastic leukemia
OT  - chronic myelogenous leukemia
OT  - eosinophilia
OT  - pre-B-cell acute lymphoblastic leukemia
EDAT- 2020/04/03 06:00
MHDA- 2021/05/28 06:00
PMCR- 2020/04/01
CRDT- 2020/04/03 06:00
PHST- 2019/11/04 00:00 [received]
PHST- 2020/02/03 00:00 [accepted]
PHST- 2020/04/03 06:00 [entrez]
PHST- 2020/04/03 06:00 [pubmed]
PHST- 2021/05/28 06:00 [medline]
PHST- 2020/04/01 00:00 [pmc-release]
AID - mcs.a004937 [pii]
AID - 10.1101/mcs.a004937 [doi]
PST - epublish
SO  - Cold Spring Harb Mol Case Stud. 2020 Apr 1;6(2):a004937. doi: 
      10.1101/mcs.a004937. Print 2020 Apr.