Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Rajala_et_al_2013

ABSTRACT: Large lymphocytic leukemia (LGL) is a chronic clonal lymphoproliferative disorder, characterized by expansion of cytotoxic CD8+ T-cells or NK-cells. We compared gene expression of 3 LGL leukemia patients with STAT3 mutation (Patients 1, 2, and 3), 3 LGL leukemia patients with STAT5b mutation (Patients 4, 5, and 6), and 2 LGL leukemia patients without STAT3/STAT5b mutation (Patients 7 and 8) with CD8 and NK-cell samples from healthy controls to assess different gene expression patterns between samples.

ORGANISM(S): Homo sapiens

SUBMITTER: Hanna Rajala

PROVIDER: E-MTAB-1611 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia.

Rajala Hanna L M HL Eldfors Samuli S Kuusanmäki Heikki H van Adrichem Arjan J AJ Olson Thomas T Lagström Sonja S Andersson Emma I EI Jerez Andres A Clemente Michael J MJ Yan Yiyi Y Zhang Dan D Awwad Andy A Ellonen Pekka P Kallioniemi Olli O Wennerberg Krister K Porkka Kimmo K Maciejewski Jaroslaw P JP Loughran Thomas P TP Heckman Caroline C Mustjoki Satu S

Blood 20130417 22

Large granular lymphocytic (LGL) leukemia is characterized by clonal expansion of cytotoxic T cells or natural killer cells. Recently, somatic mutations in the signal transducer and activator of transcription 3 (STAT3) gene were discovered in 28% to 40% of LGL leukemia patients. By exome and transcriptome sequencing of 2 STAT3 mutation-negative LGL leukemia patients, we identified a recurrent, somatic missense mutation (Y665F) in the Src-like homology 2 domain of the STAT5b gene. Targeted amplic ...[more]

PMID: 23596048

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Project description:<p>LGL leukemia can be divided into three subsets including the following: αβ or γδT-LGL and NK-LGL leukemia. All three subtypes will be enrolled using a two-stage design. The primary endpoint of the study is assessment of overall clinical response. Correlative laboratory studies will be performed aimed at determining the mechanism of response to treatment. Thirteen participants will be accrued in the first stage at a dose of 300 mg BID administered intermittently every other week (i.e., 7 days on and 7 days off). If there are two or more responders, the protocol will be extended to a second stage of the study and accrual will be extended to 25 evaluable participants. Allowing for 10% rate of ineligibility due to unexpected events and dropout, we will accrue 14 patients in the first stage and 27 patients in total. Participants that withdraw from the study for reason unrelated to toxicity, will be replaced. There are two potential stopping rules for toxicity.</p> <p>If 3 or more participants out of the 13 enrolled in the first stage experiences grade IV neurotoxicity, the study will be stopped due to excessive toxicity. Dose reductions have been incorporated for hematologic toxicity. Treatment of T and NK LGL leukemia with immunosuppressive agents such as low-dose methotrexate generally require from four to six months for a clinical response and sometimes much longer. Therefore, in participants who show clinical improvement with less than grade three toxicity, tipifarnib treatment will be continued for as many as four additional months (12 months total). After the first 8 months, response will be assessed. The protocol treatment will be discontinued in participants with progression of disease. A long-term follow up will be performed for five years in patients that receive a complete clinical response. The long-term follow up will consist of vital signs, weight, CBCs, serum chemistries, and physical examination at six month intervals.</p>

Dataset Information

Rajala_et_al_2013

Publications

Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia.

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