@entity2590 ( @entity2590 ) represent a hematologically diverse group of @entity5 , however, one subtype characterized by an isolated deletion of chromosome 5q [del(5q)] is pathologically and clinically distinct. @entity1 with del(5q) @entity2590 share biological features that account for the profound @entity417 and unique sensitivity to treatment with @entity6985 . Ineffective erythropoiesis in del(5q) @entity2590 arises from allelic deletion of the @entity52541 ( @entity52541 ) gene, which leads to @entity7465 sequestration with consequent @entity876 activation and erythroid cell death. Since its approval in 2005, @entity6985 has changed the natural course of the disease. @entity1 who achieve transfusion independence and/or a cytogenetic response with @entity6985 have a decreased risk of progression to @entity3052 and an improved overall survival compared to non-responders. Elucidation of the mechanisms of action of @entity6985 in del(5q) @entity2590 has advanced therapeutic strategies for this disease. The selective cytotoxicity of @entity6985 in del(5q) clones derives from inhibition of a haplodeficient phosphatase whose catalytic domain is encoded within the common deleted region on chromosome 5q, i.e., protein phosphatase 2A (PP2Aca). @entity4333 is a highly conserved, dual specificity phosphatase that plays an essential role in regulation of the G2/M checkpoint. Inhibition of PP2Aca results in cell-cycle arrest and apoptosis in del(5q) cells. Targeted knockdown of PP2Aca using siRNA is sufficient to sensitize non-del(5q) clones to @entity6985 . Through its inhibitory effect on @entity4333 , @entity6985 stabilizes @entity7465 to restore @entity876 degradation in erythroid precursors, with subsequent arrest in G2/M. Unfortunately, the majority of @entity1 with del(5q) @entity2590 develop resistance to @entity6985 over time associated with PP2Aca over-expression. Targeted inhibition of @entity4333 with a more potent inhibitor has emerged as an attractive therapeutic approach for @entity1 with del(5q) @entity2590 .

@entity4333 : The Achilles Heal in XXXX with 5q Deletion.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity52541 :: ('6208', 'Gene') :: ['RPS14', 'ribosomal processing S-14'] @entity417 :: ('MESH:D000740', 'Disease') :: ['hypoplastic anemia'] @entity5 :: ('MESH:D009369', 'Disease') :: ['myeloid neoplasms'] @entity7465 :: ('4193', 'Gene') :: ['MDM2'] @entity2590 :: ('MESH:D009190', 'Disease') :: ['Myelodysplastic syndromes', 'MDS'] @entity3052 :: ('MESH:D015470', 'Disease') :: ['acute myeloid leukemia'] @entity876 :: ('7157', 'Gene') :: ['p53'] @entity6985 :: ('MESH:C467567', 'Chemical') :: ['lenalidomide'] @entity4333 :: ('5524', 'Gene') :: ['PP2A']
@entity2590 :: (MESH:D009190,Disease) :: ['MDS']
