公开(公告)号：US20220411880A1

公开(公告)日：2022-12-29

申请号：US17778729

申请日：2020-11-20

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITE COTE D'AZUR ,  MEMORIAL SLOAN KETTERING CANCER CENTER ,  THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK

发明人： Laurent YVAN-CHARVET ,  Manon VIAUD ,  Alan R. TALL ,  Ross L. LEVINE ,  Omar ABDEL-WAHAB

IPC分类号： C12Q1/6886 ,  A61K31/724 ,  C07K16/28 ,  A61K38/17

摘要： In the present invention, inventors have used high throughput sequencing to identify novel mutations in ABCA1 in CM ML patient samples. Further studies in a mouse model of myelomonocytic leukemia driven by hematopoietic Tet2 deficiency have shown that these somatic mutations abrogate the tumor suppressor function of WT ABCA1, resulting in the failure to suppress canonical IL3-receptor beta signaling-driven myelopoiesis. The loss of the myelo-suppressive function of ABCA1 mutants can be overcome by raising HDL levels through overexpression of the human apolipoprotein A-1 (apoA-1) transgene. Inventors have also shown that both IL-3Rbeta blocking antibody and cyclodextrin prevented the proliferation of ABCA1 mutant-transduced Tet2 deficient BM cells similar to the effect of ABCA1-WT overexpression. Accordingly, the invention relates to a method for predicting the survival time of a subject NI suffering from CM ML comprising the step identifying at least one ABCA1 and to a method for treating said subject with HDL/ABCA recombinant (ApoA-1); cylodextrin and/or anti-IL-3Rbeta antibody.

公开(公告)号：US20210251955A1

公开(公告)日：2021-08-19

申请号：US17242530

申请日：2021-04-28

申请人： Yeda Research and Development Co. Ltd. ,  Memorial Sloan Kettering Cancer Center

发明人： Liran SHLUSH ,  Omar ABDEL-WAHAB

IPC分类号： A61K31/40 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/506 ,  A61K31/4178 ,  A61K31/34 ,  A61K31/167 ,  A61K31/454 ,  A61K31/445 ,  A61K31/4545 ,  A61K31/351 ,  A61K31/404 ,  A61K45/06 ,  A61P35/02

摘要： A method of preventing a hematopoietic disorder or malignancy in a high risk subject, the subject being positive for one or more mutation in a splicing factor, is disclosed. The method comprising administering to the subject an agent capable of inhibiting spliceosomal activity, with the proviso that said agent does not inhibit RBM39 activity.