CRLF2_sequencing_project_

I hope to gain insight into novel genetic aberrations present in these patients that will highlightimportant pathways that are involved in this subtype of leukaemia. It would be interesting to see ifthe mutations and pathways that are activated are consistent between the patients, or differencesare observed dependent upon whether the patient has the translocation or the PAR1 deletion. Ofnote is the high association with either numerical gains of chromosome X or numerical/structuralabnormalities of chromosome 21 (Down syndrome, iAMP21) in patients with CRLF2 deregulation. Ihope to find abnormalities linking chromosomes X and 21 to CRLF2 deregulation in BCP‐ALL. Byincluding the three patients that are normal for CRLF2, but have consistent genetic abnormalitiesfound in the experimental cohort, I expect to find genetic differences between these two groupsthat will help us to identify novel molecular targets specific to CRLF2 deregulation.

Type: Cancer Genomics
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 2 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001000076	CRLF2 sequencing project	Illumina HiSeq 2000	13
EGAD00001002007	To determine the clinical and genetic landscape of CRLF2 deregulated acute lymphoblastic leukaemia (CRLF2-d ALL). We identified 172 patients with a CRLF2 rearrangement treated on either the UKALL2003 trial for children and adolescents (1-24 years) or the UKALLXII trial for adolescents and adults (15-59 years). Genomic technologies from conventional karyotyping, and FISH through to whole genome and exome sequencing were used to characterise the genomes of patients with CRLF2-d ALL. This is the largest study to date to investigate the genomic landscape of CRLF2-d ALL and define CRLF2-d as a unique subgroup of B-other ALL. We have confirmed the high incidence of CRLF2-d in Down syndrome-ALL and demonstrated the co-existence of CRLF2-d with other primary chromosomal rearrangements, suggesting that in these patients CRLF2-d can be a secondary genetic abnormality. Other defining features included enrichment of IKZF1, BTG1 and ADD3 deletions in IGH-CRLF2 patients and specific chromosomal gains seen at much higher frequencies than B-other ALL . We report recurrent established and new co-operating abnormalities and the novel involvement of USP9X and DDX3X in CRLF2-d ALL. It is clear from these data that CRLF2-d ALL is heterogenoeus, requiring a combination of genetic abnormalities in functionally relevent genes, to work alongside the deregulated expression of CRLF2 in order to initiate and drive leukaemogenesis in this subtype. Although the functional relevance of many of the abnormalities presented here are currently unknown, many are likely to activate alternate pathways or sensitize patients to current therapies.	Illumina HiSeq 2000	11

Publications	Citations
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 56: 2017 363-372	27
Chemotherapy induces canalization of cell state in childhood B-cell precursor acute lymphoblastic leukemia. Turati VA, Guerra-Assunção JA, Potter NE, Gupta R, Ecker S, Daneviciute A, Tarabichi M, Webster AP, Ding C, May G, James C, Brown J, Conde L, Russell LJ, Ancliff P, Inglott S, Cazzaniga G, Biondi A, Hall GW, Lynch M, Hubank M, Macaulay I, Beck S, Van Loo P, Jacobsen SE, Greaves M, Herrero J, Enver T. Nat Cancer 2: 2021 835-852	14

Publications

Citations

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 56: 2017 363-372

Chemotherapy induces canalization of cell state in childhood B-cell precursor acute lymphoblastic leukemia.
Turati VA, Guerra-Assunção JA, Potter NE, Gupta R, Ecker S, Daneviciute A, Tarabichi M, Webster AP, Ding C, May G, James C, Brown J, Conde L, Russell LJ, Ancliff P, Inglott S, Cazzaniga G, Biondi A, Hall GW, Lynch M, Hubank M, Macaulay I, Beck S, Van Loo P, Jacobsen SE, Greaves M, Herrero J, Enver T. Nat Cancer 2: 2021 835-852