Dataset Information

PCGP Ph-likeALL GEA - samples

ABSTRACT: PCGP Ph-likeALL GEA

PROVIDER: EGAD00010000596 | EGA |

REPOSITORIES: EGA

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Publications

Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia.

Roberts Kathryn G KG Li Yongjin Y Payne-Turner Debbie D Harvey Richard C RC Yang Yung-Li YL Pei Deqing D McCastlain Kelly K Ding Li L Lu Charles C Song Guangchun G Ma Jing J Becksfort Jared J Rusch Michael M Chen Shann-Ching SC Easton John J Cheng Jinjun J Boggs Kristy K Santiago-Morales Natalia N Iacobucci Ilaria I Fulton Robert S RS Wen Ji J Valentine Marcus M Cheng Cheng C Paugh Steven W SW Devidas Meenakshi M Chen I-Ming IM Reshmi Shalini S Smith Amy A Hedlund Erin E Gupta Pankaj P Nagahawatte Panduka P Wu Gang G Chen Xiang X Yergeau Donald D Vadodaria Bhavin B Mulder Heather H Winick Naomi J NJ Larsen Eric C EC Carroll William L WL Heerema Nyla A NA Carroll Andrew J AJ Grayson Guy G Tasian Sarah K SK Moore Andrew S AS Keller Frank F Frei-Jones Melissa M Whitlock James A JA Raetz Elizabeth A EA White Deborah L DL Hughes Timothy P TP Guidry Auvil Jaime M JM Smith Malcolm A MA Marcucci Guido G Bloomfield Clara D CD Mrózek Krzysztof K Kohlschmidt Jessica J Stock Wendy W Kornblau Steven M SM Konopleva Marina M Paietta Elisabeth E Pui Ching-Hon CH Jeha Sima S Relling Mary V MV Evans William E WE Gerhard Daniela S DS Gastier-Foster Julie M JM Mardis Elaine E Wilson Richard K RK Loh Mignon L ML Downing James R JR Hunger Stephen P SP Willman Cheryl L CL Zhang Jinghui J Mullighan Charles G CG

The New England journal of medicine 20140901 11

<h4>Background</h4>Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults.<h4>Methods</h4>We performed genomic profiling of 1725 patients with precursor ...[more]

PMID: 25207766

Publication: 1/2

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Project description:We aim to compare the genomic discrepancies across de novo Ph+ ALL, Ph+ MPAL and Ph+ AML, three diseases characterized by the occurrence of BCR-ABL1 transcripts but showing varied immunophenotypes. The data we are now submitting is the genomic copy number variants of these three groups. The following is the abstract with associated manuscript. The chromosome abnormality of Philadelphia (Ph) is typically seen in de novo acute lymphoblastic leukemia (ALL). It has also been identified in mixed phenotype acute leukemia (MPAL) and acute myeloid leukemia (AML) in the revisions to World Health Organization classification of myeloid neoplasms and actue leukemia. The discrepancies between these patients and potential mechanisms underlying differentiation fate of the leukemia cells remain poorly defined. We evaluated the clinical, genomic and transcriptomic features of Ph+ ALL, Ph+ MPAL and Ph+ AML by taking advantage of high-density genomic analysis, including next-generation sequencing array comparative genomic hybridization and gene expression profiling for transcriptomic analysis. Our results showed that the three cohorts demonstrated diversified clinical features. Ph+ ALL had the best response to induction therapy, with a complete remission (CR) rate of 93.5 and molecular response of 43.5%. Ph+ MPAL had a 90.0% CR rate but only 5.9% of molecular response. The CR rate of Ph+ AML was only 68.8%. Ph+ ALL was characterized by loss and mutations of B-cell development gene IKZF1 and PAX5, and frequent histone H3K36 trimethyltransferase SETD2 mutations. SETD2 mutations were detected in 11.3% of Ph+ ALL patients and predicted higher relapse rate. Ph+ MPAL and Ph+ AML featured high frequency of RUNX1 mutations. Further studies showed RUNX1-R177X mutation inhibited 32D cell differentiation induced by G-Csf, and cooperated with BCR-ABL1 to lead to myeloid differentiation arrest of human cord blood CD34+ cells. It is therefore presumed that these additional mutations work in synergy with BCR-ABL1 fusion gene to facilitate the development of Ph-positive acute leukemia in different immunophenotypic classifications.

Dataset Information

PCGP Ph-likeALL GEA - samples

Publications

Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia.

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