Mutations in TLR/MYD88 pathway identify a subset of young chronic lymphocytic leukemia patients with favorable outcome

Blood ◽  
2014 ◽  
Vol 123 (24) ◽  
pp. 3790-3796 ◽  
Author(s):  
Alejandra Martínez-Trillos ◽  
Magda Pinyol ◽  
Alba Navarro ◽  
Marta Aymerich ◽  
Pedro Jares ◽  
...  

Key Points Mutations in the TLR/MYD88 pathway occur in 4% of patients with CLL, and they are the most frequent in young patients. TLR/MYD88 mutations in CLL patients confer a good outcome, which is similar to that of the age- and gender-matched healthy population.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7086-7086
Author(s):  
Christopher Flowers ◽  
Charles Michael Farber ◽  
Ian Flinn ◽  
David L. Grinblatt ◽  
Neil E. Kay ◽  
...  

7086 Background: The HRQOL of patients (pts) with chronic lymphocytic leukemia (CLL) has not been adequately delineated across patient, disease and treatment characteristics. We evaluated HRQOL of CLL pts undergoing treatment in the United States (US) by age, gender and line of therapy. Methods: Data were collected in Connect CLL, a prospective observational US registry. Physicians provided data on demographics, clinical characteristics and line of therapy at enrollment. HRQOL was self-reported by pts at enrollment using the Functional Assessment of Cancer Therapy-Leukemia, an instrument that yields a leukemia-specific total HRQOL score (FACT-Leu) and a cancer-specific total HRQOL score (FACT-G). Mean total scores were analyzed by line of therapy, age and gender. Statistical significance was ascertained by ANOVA using SAS 9.2. Multivariate analyses were conducted to assess the relative association of line of therapy, age and gender with HRQOL. Results: Among 1,252 pts enrolled from 161 geographically diverse centers (90% community, 8% academic, 2% veterans/military), pts were predominantly male (63%), white (89%) with mean age 69 yrs. Pts were categorized by line of therapy at enrollment: First 61%, Second 18%, Third 11%, Higher 9%; and by age group: <65 33%, 65-74 35%, 75+ 32%. Univariate analyses suggested that the total FACT-Leu score was significantly better in men than women (P=0.004); in pts aged 65-74 vs younger or older pts (P=0.033); and in pts initiating first-line treatment vs pts receiving subsequent treatments (P=0.0002). Similar results were found with the FACT-G score except that gender differences were not statistically significant. Multivariate analysis confirmed that line of therapy (P=0.007), gender (P<0.0001), and age group (P=0.039) were each associated with significant differences in the FACT-Leu total score. Conclusions: Results from the Connect CLL Registry indicate that HRQOL is better among pts initiating first-line therapy compared to pts initiating subsequent treatments, and that this remains true when age and gender are considered. Future analyses should determine how HRQOL may change over time relative to treatment and treatment response.


Blood ◽  
2013 ◽  
Vol 121 (14) ◽  
pp. 2704-2714 ◽  
Author(s):  
Alan G. Ramsay ◽  
Rachel Evans ◽  
Shahryar Kiaii ◽  
Lena Svensson ◽  
Nancy Hogg ◽  
...  

Key Points CLL cells induce defects in T-cell LFA-1–mediated migration by altering Rho GTPase activation signaling, downregulating RhoA and Rac1, and upregulating Cdc42. Lenalidomide repairs these T-cell defects by restoring normal Rho GTPase activation signaling.


Blood ◽  
2014 ◽  
Vol 124 (3) ◽  
pp. 453-462 ◽  
Author(s):  
Mohini Rajasagi ◽  
Sachet A. Shukla ◽  
Edward F. Fritsch ◽  
Derin B. Keskin ◽  
David DeLuca ◽  
...  

Key Points Tumor neoantigens are a promising class of immunogens based on exquisite tumor specificity and the lack of central tolerance against them. Massively parallel DNA sequencing with class I prediction enables systematic identification of tumor neoepitopes (including from CLL).


2020 ◽  
Vol 4 (24) ◽  
pp. 6169-6174
Author(s):  
Qianze Dong ◽  
Yan Xiu ◽  
Aaron Bossler ◽  
Sergei Syrbu ◽  
Hongming Wang ◽  
...  

Key Points Common progenitor cells exist in clonally related concomitant chronic lymphocytic leukemia and acute myeloid leukemias. CLL cells dedifferentiated to clonally related myeloid cells posttransplantation.


Blood ◽  
2014 ◽  
Vol 123 (16) ◽  
pp. e37-e45 ◽  
Author(s):  
Lukas M. Simon ◽  
Leonard C. Edelstein ◽  
Srikanth Nagalla ◽  
Angela B. Woodley ◽  
Edward S. Chen ◽  
...  

Key Points Unique dataset of human platelet mRNA, miRNA, and physiology reveals mRNAs and miRNAs that differ by age and gender. Interactive public web tool (www.plateletomics.com) provides biologic insights into platelet function and gene expression.


Blood ◽  
2018 ◽  
Vol 132 (2) ◽  
pp. 170-178 ◽  
Author(s):  
Md Kamrul Hasan ◽  
Jian Yu ◽  
George F. Widhopf ◽  
Laura Z. Rassenti ◽  
Liguang Chen ◽  
...  

Key Points Wnt5a enhances activation of Rac1/2 by inducing ROR1 to interact with DOCK2. ROR1-DOCK2 interaction contributes to Wnt5a-enhanced CLL cell proliferation.


Blood ◽  
2018 ◽  
Vol 131 (23) ◽  
pp. 2541-2551 ◽  
Author(s):  
Geffen Kleinstern ◽  
Nicola J. Camp ◽  
Lynn R. Goldin ◽  
Celine M. Vachon ◽  
Claire M. Vajdic ◽  
...  

Key Points PRS, based on the known CLL loci, predicts CLL risk with high discrimination. This PRS predicts risk of monoclonal B-cell lymphocytosis, a precursor to CLL and a condition that has clinical impact beyond risk for CLL.


Blood ◽  
2016 ◽  
Vol 127 (5) ◽  
pp. 582-595 ◽  
Author(s):  
Marwan Kwok ◽  
Nicholas Davies ◽  
Angelo Agathanggelou ◽  
Edward Smith ◽  
Ceri Oldreive ◽  
...  

Key PointsATR inhibition is synthetically lethal to TP53- or ATM-defective CLL cells. ATR targeting induces selective cytotoxicity and chemosensitization in TP53- or ATM-defective CLL cells in vitro and in vivo.


Blood ◽  
2013 ◽  
Vol 121 (24) ◽  
pp. 4902-4905 ◽  
Author(s):  
Davide Rossi ◽  
Valeria Spina ◽  
Riccardo Bomben ◽  
Silvia Rasi ◽  
Michele Dal-Bo ◽  
...  

Key Points BCR subsets 2 and 8 show specific genetic profiles influencing CLL course.


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