ABSTRACT
With imatinib still being linked to the breakthrough in CML therapy and probably being the most prescribed drug, second-generation TKIs are increasingly gaining importance. Showing higher response rates while not leading to more adverse events, nilotinib has become an attractive option in the first-line treatment of chronic-phase chronic myeloid leukemia. By reaching deep and long-lasting molecular remissions, discontinuation of TKIs is becoming one of the central topics of future CML therapy. Stopping nilotinib seems safe and provides a stable remission in about half of the eligible patients, though long-term data are still missing.
Subject(s)
Antineoplastic Agents/pharmacology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , HumansSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fusion Proteins, bcr-abl/genetics , Hematopoietic Stem Cell Transplantation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , RNA, Messenger/genetics , RNA-Binding Proteins/genetics , Aged , Dasatinib/therapeutic use , Disease Progression , Female , Fusion Proteins, bcr-abl/metabolism , Gene Expression , Humans , Imatinib Mesylate/therapeutic use , Interferons/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Longitudinal Studies , Male , Middle Aged , Mutation , Pyrimidines/therapeutic use , RNA, Messenger/metabolism , RNA-Binding Proteins/metabolism , Retrospective Studies , Survival AnalysisABSTRACT
A better understanding of events triggering chronic myeloid leukemia progression is critical for optimized clinical management of chronic myeloid leukemia (CML). We sought to validate that increased expression of Musashi 2 (MSI2), a post-transcription regulator, is associated with progression and prognosis. Screening of 152 patients with CML showed that MSI2 was significantly decreased among patients with CML in chronic phase (CP) at diagnosis (p < 0.0001), but found no significant difference between the normal control group and treated patients with CML in CP. Moreover MSI2 was significantly increased (p < 0.0001) in patients with advance disease (AD) CML. Furthermore, our human hematopoietic cell line data imply that MSI2 and BCR-ABL1 mRNA expression are correlated. However, these data cast a doubt on earlier reports that MSI2 effects HES1 expression via NUMB-NOTCH signaling.
Subject(s)
Gene Expression Regulation, Leukemic , Hematopoietic Stem Cells/metabolism , Leukemia, Myeloid, Chronic-Phase/metabolism , Leukemia, Myeloid, Chronic-Phase/pathology , RNA-Binding Proteins/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Child , Disease Progression , Female , Follow-Up Studies , Fusion Proteins, bcr-abl/genetics , Hematopoietic Stem Cells/pathology , Humans , Immunoenzyme Techniques , Leukemia, Myeloid, Chronic-Phase/genetics , Leukemia, Myeloid, Chronic-Phase/mortality , Male , Middle Aged , Neoplasm Staging , Prognosis , RNA, Messenger/genetics , RNA-Binding Proteins/genetics , Real-Time Polymerase Chain Reaction , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , Survival Rate , Up-Regulation , Young AdultABSTRACT
Chronic myeloid leukemia developing after transplantation of solid organs and concomitant immunosuppression is a rare but still significant clinical phenomenon. We here describe an additional case of a 62-year-old male patient developing CML after orthotopic heart transplantation and medication with cyclosporine A, mofetil-mycophenolate, and steroids. Initial antileukemic therapy was imatinib at a standard dose and within 15 months of therapy a complete cytogenetic response was noted. In this report we discuss the clinical implications of these rare but biologically important cases.
