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CRLF2 Gene Rearrangement

MedGen UID:
1387247
•Concept ID:
C4321510
•
Cell or Molecular Dysfunction
Synonyms: CRLF2 Rearrangement; Cytokine Receptor Crl2 Gene Rearrangement; Cytokine Receptor Like Factor 2 Gene Rearrangement; Cytokine Receptor-Like Factor 2 Gene Rearrangement; Thymic Stromal-Derived Lymphopoietin Receptor Gene Rearrangement; TSLPR Gene Rearrangement

Definition

A molecular abnormality indicating rearrangement of the CRLF2 gene. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCRLF2 Gene Rearrangement

Professional guidelines

PubMed

Genomics in acute lymphoblastic leukaemia: insights and treatment implications.
Roberts KG, Mullighan CG
Nat Rev Clin Oncol 2015 Jun;12(6):344-57. Epub 2015 Mar 17 doi: 10.1038/nrclinonc.2015.38. PMID: 25781572

Recent clinical studies

Etiology

Emerging molecular subtypes and therapies in acute lymphoblastic leukemia.
Davis K, Sheikh T, Aggarwal N
Semin Diagn Pathol 2023 May;40(3):202-215. Epub 2023 Apr 9 doi: 10.1053/j.semdp.2023.04.003. PMID: 37120350
High occurrence of CRLF2 abnormalities in Mexican children with B-cell acute lymphoblastic leukemia.
Juárez-Velázquez MDR, Moreno-Lorenzana DL, Martínez Anaya DA, Hernández Monterde EA, Aguilar-Hernández MM, Reyes-León A, Chávez-González MA, López Santiago N, Zapata Tarrés M, Juárez Villegas L, Rivera Sánchez N, Soto Lerma O, Vega-Vega L, Rivera Luna R, Pérez-Vera P
Cytokine 2022 Jul;155:155896. Epub 2022 May 7 doi: 10.1016/j.cyto.2022.155896. PMID: 35537330
Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's Oncology Group.
Reshmi SC, Harvey RC, Roberts KG, Stonerock E, Smith A, Jenkins H, Chen IM, Valentine M, Liu Y, Li Y, Shao Y, Easton J, Payne-Turner D, Gu Z, Tran TH, Nguyen JV, Devidas M, Dai Y, Heerema NA, Carroll AJ 3rd, Raetz EA, Borowitz MJ, Wood BL, Angiolillo AL, Burke MJ, Salzer WL, Zweidler-McKay PA, Rabin KR, Carroll WL, Zhang J, Loh ML, Mullighan CG, Willman CL, Gastier-Foster JM, Hunger SP
Blood 2017 Jun 22;129(25):3352-3361. Epub 2017 Apr 13 doi: 10.1182/blood-2016-12-758979. PMID: 28408464Free PMC Article
Characterisation of the genomic landscape of CRLF2-rearranged acute lymphoblastic leukemia.
Russell LJ, Jones L, Enshaei A, Tonin S, Ryan SL, Eswaran J, Nakjang S, Papaemmanuil E, Tubio JM, Fielding AK, Vora A, Campbell PJ, Moorman AV, Harrison CJ
Genes Chromosomes Cancer 2017 May;56(5):363-372. Epub 2017 Jan 18 doi: 10.1002/gcc.22439. PMID: 28033648Free PMC Article
High CRLF2 expression associates with IKZF1 dysfunction in adult acute lymphoblastic leukemia without CRLF2 rearrangement.
Ge Z, Gu Y, Zhao G, Li J, Chen B, Han Q, Guo X, Liu J, Li H, Yu MD, Olson J, Steffens S, Payne KJ, Song C, Dovat S
Oncotarget 2016 Aug 2;7(31):49722-49732. doi: 10.18632/oncotarget.10437. PMID: 27391346Free PMC Article

Diagnosis

Emerging molecular subtypes and therapies in acute lymphoblastic leukemia.
Davis K, Sheikh T, Aggarwal N
Semin Diagn Pathol 2023 May;40(3):202-215. Epub 2023 Apr 9 doi: 10.1053/j.semdp.2023.04.003. PMID: 37120350
Genome-wide CRISPR-Cas9 screen identifies rationally designed combination therapies for CRLF2-rearranged Ph-like ALL.
Sasaki K, Yamauchi T, Semba Y, Nogami J, Imanaga H, Terasaki T, Nakao F, Akahane K, Inukai T, Verhoeyen E, Akashi K, Maeda T
Blood 2022 Feb 3;139(5):748-760. doi: 10.1182/blood.2021012976. PMID: 34587248Free PMC Article
CRLF2 and IKZF1 abnormalities in Mexican children with acute lymphoblastic leukemia and recurrent gene fusions: exploring surrogate markers of signaling pathways.
Moreno Lorenzana D, Juárez Velázquez MDR, Reyes León A, Martínez Anaya D, Hernández Monterde A, Salas Labadía C, Navarrete Meneses MDP, Zapata Tarrés M, Juárez Villegas L, Jarquín Ramírez B, Cárdenas Cardós R, Herrera Almanza M, Paredes Aguilera R, Pérez Vera P
J Pathol Clin Res 2021 Jul;7(4):410-421. Epub 2021 Apr 23 doi: 10.1002/cjp2.211. PMID: 33890726Free PMC Article
Philadelphia Chromosome-like Acute Lymphoblastic Leukemia.
Pui CH, Roberts KG, Yang JJ, Mullighan CG
Clin Lymphoma Myeloma Leuk 2017 Aug;17(8):464-470. doi: 10.1016/j.clml.2017.03.299. PMID: 28842136Free PMC Article
Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's Oncology Group.
Reshmi SC, Harvey RC, Roberts KG, Stonerock E, Smith A, Jenkins H, Chen IM, Valentine M, Liu Y, Li Y, Shao Y, Easton J, Payne-Turner D, Gu Z, Tran TH, Nguyen JV, Devidas M, Dai Y, Heerema NA, Carroll AJ 3rd, Raetz EA, Borowitz MJ, Wood BL, Angiolillo AL, Burke MJ, Salzer WL, Zweidler-McKay PA, Rabin KR, Carroll WL, Zhang J, Loh ML, Mullighan CG, Willman CL, Gastier-Foster JM, Hunger SP
Blood 2017 Jun 22;129(25):3352-3361. Epub 2017 Apr 13 doi: 10.1182/blood-2016-12-758979. PMID: 28408464Free PMC Article

Therapy

CRLF2 rearrangement in Ph-like acute lymphoblastic leukemia predicts relative glucocorticoid resistance that is overcome with MEK or Akt inhibition.
Meyer LK, Delgado-Martin C, Maude SL, Shannon KM, Teachey DT, Hermiston ML
PLoS One 2019;14(7):e0220026. Epub 2019 Jul 18 doi: 10.1371/journal.pone.0220026. PMID: 31318944Free PMC Article
The biology of Philadelphia chromosome-like ALL.
Roberts KG
Best Pract Res Clin Haematol 2017 Sep;30(3):212-221. Epub 2017 Jul 6 doi: 10.1016/j.beha.2017.07.003. PMID: 29050694
Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's Oncology Group.
Reshmi SC, Harvey RC, Roberts KG, Stonerock E, Smith A, Jenkins H, Chen IM, Valentine M, Liu Y, Li Y, Shao Y, Easton J, Payne-Turner D, Gu Z, Tran TH, Nguyen JV, Devidas M, Dai Y, Heerema NA, Carroll AJ 3rd, Raetz EA, Borowitz MJ, Wood BL, Angiolillo AL, Burke MJ, Salzer WL, Zweidler-McKay PA, Rabin KR, Carroll WL, Zhang J, Loh ML, Mullighan CG, Willman CL, Gastier-Foster JM, Hunger SP
Blood 2017 Jun 22;129(25):3352-3361. Epub 2017 Apr 13 doi: 10.1182/blood-2016-12-758979. PMID: 28408464Free PMC Article
Molecular characterization of acute lymphoblastic leukemia with high CRLF2 gene expression in childhood.
Schmäh J, Fedders B, Panzer-Grümayer R, Fischer S, Zimmermann M, Dagdan E, Bens S, Schewe D, Moericke A, Alten J, Bleckmann K, Siebert R, Schrappe M, Stanulla M, Cario G
Pediatr Blood Cancer 2017 Oct;64(10) Epub 2017 Apr 1 doi: 10.1002/pbc.26539. PMID: 28371317
Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia.
Harvey RC, Mullighan CG, Chen IM, Wharton W, Mikhail FM, Carroll AJ, Kang H, Liu W, Dobbin KK, Smith MA, Carroll WL, Devidas M, Bowman WP, Camitta BM, Reaman GH, Hunger SP, Downing JR, Willman CL
Blood 2010 Jul 1;115(26):5312-21. Epub 2010 Feb 4 doi: 10.1182/blood-2009-09-245944. PMID: 20139093Free PMC Article

Prognosis

High occurrence of CRLF2 abnormalities in Mexican children with B-cell acute lymphoblastic leukemia.
Juárez-Velázquez MDR, Moreno-Lorenzana DL, Martínez Anaya DA, Hernández Monterde EA, Aguilar-Hernández MM, Reyes-León A, Chávez-González MA, López Santiago N, Zapata Tarrés M, Juárez Villegas L, Rivera Sánchez N, Soto Lerma O, Vega-Vega L, Rivera Luna R, Pérez-Vera P
Cytokine 2022 Jul;155:155896. Epub 2022 May 7 doi: 10.1016/j.cyto.2022.155896. PMID: 35537330
Molecular characterization of acute lymphoblastic leukemia with high CRLF2 gene expression in childhood.
Schmäh J, Fedders B, Panzer-Grümayer R, Fischer S, Zimmermann M, Dagdan E, Bens S, Schewe D, Moericke A, Alten J, Bleckmann K, Siebert R, Schrappe M, Stanulla M, Cario G
Pediatr Blood Cancer 2017 Oct;64(10) Epub 2017 Apr 1 doi: 10.1002/pbc.26539. PMID: 28371317
Characterisation of the genomic landscape of CRLF2-rearranged acute lymphoblastic leukemia.
Russell LJ, Jones L, Enshaei A, Tonin S, Ryan SL, Eswaran J, Nakjang S, Papaemmanuil E, Tubio JM, Fielding AK, Vora A, Campbell PJ, Moorman AV, Harrison CJ
Genes Chromosomes Cancer 2017 May;56(5):363-372. Epub 2017 Jan 18 doi: 10.1002/gcc.22439. PMID: 28033648Free PMC Article
High CRLF2 expression associates with IKZF1 dysfunction in adult acute lymphoblastic leukemia without CRLF2 rearrangement.
Ge Z, Gu Y, Zhao G, Li J, Chen B, Han Q, Guo X, Liu J, Li H, Yu MD, Olson J, Steffens S, Payne KJ, Song C, Dovat S
Oncotarget 2016 Aug 2;7(31):49722-49732. doi: 10.18632/oncotarget.10437. PMID: 27391346Free PMC Article
Improving outcomes for high-risk ALL: translating new discoveries into clinical care.
Hunger SP, Raetz EA, Loh ML, Mullighan CG
Pediatr Blood Cancer 2011 Jun;56(6):984-93. Epub 2011 Feb 15 doi: 10.1002/pbc.22996. PMID: 21370430

Clinical prediction guides

CRLF2 and IKZF1 abnormalities in Mexican children with acute lymphoblastic leukemia and recurrent gene fusions: exploring surrogate markers of signaling pathways.
Moreno Lorenzana D, Juárez Velázquez MDR, Reyes León A, Martínez Anaya D, Hernández Monterde A, Salas Labadía C, Navarrete Meneses MDP, Zapata Tarrés M, Juárez Villegas L, Jarquín Ramírez B, Cárdenas Cardós R, Herrera Almanza M, Paredes Aguilera R, Pérez Vera P
J Pathol Clin Res 2021 Jul;7(4):410-421. Epub 2021 Apr 23 doi: 10.1002/cjp2.211. PMID: 33890726Free PMC Article
CRLF2 rearrangement in Ph-like acute lymphoblastic leukemia predicts relative glucocorticoid resistance that is overcome with MEK or Akt inhibition.
Meyer LK, Delgado-Martin C, Maude SL, Shannon KM, Teachey DT, Hermiston ML
PLoS One 2019;14(7):e0220026. Epub 2019 Jul 18 doi: 10.1371/journal.pone.0220026. PMID: 31318944Free PMC Article
Characterisation of the genomic landscape of CRLF2-rearranged acute lymphoblastic leukemia.
Russell LJ, Jones L, Enshaei A, Tonin S, Ryan SL, Eswaran J, Nakjang S, Papaemmanuil E, Tubio JM, Fielding AK, Vora A, Campbell PJ, Moorman AV, Harrison CJ
Genes Chromosomes Cancer 2017 May;56(5):363-372. Epub 2017 Jan 18 doi: 10.1002/gcc.22439. PMID: 28033648Free PMC Article
High CRLF2 expression associates with IKZF1 dysfunction in adult acute lymphoblastic leukemia without CRLF2 rearrangement.
Ge Z, Gu Y, Zhao G, Li J, Chen B, Han Q, Guo X, Liu J, Li H, Yu MD, Olson J, Steffens S, Payne KJ, Song C, Dovat S
Oncotarget 2016 Aug 2;7(31):49722-49732. doi: 10.18632/oncotarget.10437. PMID: 27391346Free PMC Article
Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia.
Harvey RC, Mullighan CG, Chen IM, Wharton W, Mikhail FM, Carroll AJ, Kang H, Liu W, Dobbin KK, Smith MA, Carroll WL, Devidas M, Bowman WP, Camitta BM, Reaman GH, Hunger SP, Downing JR, Willman CL
Blood 2010 Jul 1;115(26):5312-21. Epub 2010 Feb 4 doi: 10.1182/blood-2009-09-245944. PMID: 20139093Free PMC Article

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