Acute myeloid leukemia (AML) is recognized as a complex disease of hematopoietic stem cell disorders, but its pathogenesis mechanisms, diagnosis, and treatment remain unclear. General histone deacetylase (HDAC) inhibitors have been used in blood cancers including AML, but the lack of gene specificity greatly limits their anti-cancer effects and clinical applications. Here, we found that HDAC1 expression was negatively correlated with that of Krüppel-like factor 4 (Klf4) and that AML patients with lower HDAC1 level had better prognosis. Further, knockdown of HDAC1 in leukemia cells K562, HL-60, and U937 significantly increased Klf4 expression and inhibited cell cycle progression and cell proliferation, similar results were found for HDAC inhibitors (VPA and mocetinostat). Moreover, overexpression or knockdown of Klf4 could markedly block the effects of HDAC1 overexpression or knockdown on leukemia cells in vitro and in vivo, respectively. Mechanistic analyses demonstrated that HDAC1 and Klf4 competitively bound to the promoter region of Klf4 and oppositely regulated Klf4 expression in myeloid leukemia. We identified HDAC1 as a potential specific target for repressing cell proliferation and inducing cell cycle arrest through interplay and modulation of Klf4 expression, suggests that HDAC1 and Klf4 are potential new molecular markers and targets for clinical diagnosis, prognosis, and treatment of myeloid leukemia.

Large-scale sequencing studies on glioblastoma have identified numerous genetic alterations.Leucine-zipper-like transcription regulator 1 (LZTR1) is inactivated by non-synonymous mutations and copy number losses, suggesting that it is a tumor suppressor in glioblastoma.However, how LZTR1 mutations contribute to glioblastoma pathogenesis remains poorly understood. Here, we revealed that LZTR1, as an adaptor of the CUL3 E3 ubiquitin ligase complex, recognizes and triggers ubiquitin-dependent degradation of oncoprotein RIT1, a RAS-like GTPase. Wild-type LZTR1 suppresses glioblastoma cell proliferation and migration by inactivating the MAPK/ERK signaling pathway in a RIT1-dependent manner. However, the effects were abrogated by the glioblastoma-associated LZTR1 mutations. Our findings revealed the underlying molecular mechanism of LZTR1 mutations-driven glioblastoma, and provide novel therapeutic target for LZTR1 mutations-driven glioblastoma.

Excess weight was associated with increased risk of brain tumors and meningiomas but not with gliomas. Selective screening for brain tumors among obesity, especially for the females, might be more instructive.

INTRODUCTIONPosterior hemivertebra resection combined with multisegmental or bisegmental fusion has been applied successfully for congenital scoliosis. However, there are several immature bones and their growth can be influenced by long segmental fusion in congenital patients. Posterior hemivertebra resection and monosegmental fusion was therefore suggested for treatment of congenital scoliosis caused by hemivertebra.METHODSBetween June 2001 and June 2010, 60 congenital scoliosis patients (aged 2–18 years) who underwent posterior hemivertebra resection and monosegmental fusion were enrolled in our study. A standing anteroposterior x-ray of the whole spine was obtained preoperatively, postoperatively and at the last follow-up appointment to analyse the Cobb angle in the coronal and sagittal planes as well as the trunk shift.RESULTSThe mean preoperative coronal plane Cobb angle was 41.6º. This was corrected to 5.1º postoperatively and 5.3º at the last follow-up visit (correction 87.3%). The compensatory cranial curve was improved from 18.1º preoperatively to 7.1º postoperatively and 6.5º at the last follow-up visit while the compensatory caudal curve was improved from 21.5º to 6.1º after surgery and 5.6º at the last follow-up visit. The mean sagittal plane Cobb angle was 23.3º before surgery, 7.3º after surgery and 6.8º at the last follow-up visit (correction 70.1%). The trunk shift of 18.5mm was improved to 15.2mm.CONCLUSIONSPosterior hemivertebra resection and monosegmental fusion seems to be an effective approach for treatment of congenital scoliosis caused by hemivertebra, allowing for excellent correction in both the frontal and sagittal planes.