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Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia

Mullighan, Charles G ; Collins-Underwood, J Racquel ; Phillips, Letha A A ; Loudin, Michael G ; Liu, Wei ; Zhang, Jinghui ; Ma, Jing ; Coustan-Smith, Elaine ; Harvey, Richard C ; Willman, Cheryl L ; Mikhail, Fady M ; Meyer, Julia ; Carroll, Andrew J ; Williams, Richard T ; Cheng, Jinjun ; Heerema, Nyla A ; Basso, Giuseppe ; Pession, Andrea ; Pui, Ching-Hon ; Raimondi, Susana C ; Hunger, Stephen P ; Downing, James R ; Carroll, William L ; Rabin, Karen R

Nature genetics, 2009-11, Vol.41 (11), p.1243-1246 [Periódico revisado por pares]

New York, NY: Nature Publishing Group

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Título:
Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia
Autor: Mullighan, Charles G ; Collins-Underwood, J Racquel ; Phillips, Letha A A ; Loudin, Michael G ; Liu, Wei ; Zhang, Jinghui ; Ma, Jing ; Coustan-Smith, Elaine ; Harvey, Richard C ; Willman, Cheryl L ; Mikhail, Fady M ; Meyer, Julia ; Carroll, Andrew J ; Williams, Richard T ; Cheng, Jinjun ; Heerema, Nyla A ; Basso, Giuseppe ; Pession, Andrea ; Pui, Ching-Hon ; Raimondi, Susana C ; Hunger, Stephen P ; Downing, James R ; Carroll, William L ; Rabin, Karen R
Assuntos: Acute lymphocytic leukemia ; Amino Acid Sequence ; Animals ; Base Sequence ; Biological and medical sciences ; Cancer ; Cell cycle ; Cell Line ; Chromosome aberrations ; Chromosome Deletion ; Down syndrome ; Down Syndrome - complications ; Down Syndrome - genetics ; Fundamental and applied biological sciences. Psychology ; Gene mutations ; Gene Rearrangement ; Genetic aspects ; Genetics ; Genetics of eukaryotes. Biological and molecular evolution ; Genomics ; Health aspects ; Hematologic and hematopoietic diseases ; Hospitals ; Humans ; Janus Kinase 2 - genetics ; Janus Kinase 2 - metabolism ; Kinases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical genetics ; Medical research ; Medical sciences ; Mice ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Receptors, Cytokine - chemistry ; Receptors, Cytokine - genetics ; Receptors, Cytokine - metabolism ; Receptors, Purinergic P2 - genetics ; Receptors, Purinergic P2 - metabolism ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - metabolism ; Risk factors ; Studies
É parte de: Nature genetics, 2009-11, Vol.41 (11), p.1243-1246
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SourceType-Scholarly Journals-1
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Descrição: Aneuploidy and translocations are hallmarks of B-progenitor acute lymphoblastic leukemia (ALL), but many individuals with this cancer lack recurring chromosomal alterations. Here we report a recurring interstitial deletion of the pseudoautosomal region 1 of chromosomes X and Y in B-progenitor ALL that juxtaposes the first, noncoding exon of P2RY8 with the coding region of CRLF2. We identified the P2RY8-CRLF2 fusion in 7% of individuals with B-progenitor ALL and 53% of individuals with ALL associated with Down syndrome. CRLF2 alteration was associated with activating JAK mutations, and expression of human P2RY8-CRLF2 together with mutated mouse Jak2 resulted in constitutive Jak-Stat activation and cytokine-independent growth of Ba/F3 cells overexpressing interleukin-7 receptor alpha. Our findings indicate that these two genetic lesions together contribute to leukemogenesis in B-progenitor ALL.
Editor: New York, NY: Nature Publishing Group
Idioma: Inglês

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Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia

New York, NY: Nature Publishing Group

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