Therapeutic Response and Prognosis of Adult Acute Myeloid Leukemia with Chromosome Karyotype Abnormalities / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and prognosis of acute myeloid leukemia (AML) patients with chromosome karyotype abnormalities.@*METHODS@#The clinical features and treatment responses of 91 patients with AML were collected and analyzed retrospectively. The efficacy and survival rate of the AML patients with normal and abnormal chromosome karyotype were compared.@*RESULTS@#Chromosome translocations and monosomal karyotypes were the main heterogeneity of AML. There was no significant difference in complete remission rate and overall response rate between the normal and abnormal karyotype groups, but the recurrence rate was higher in abnormal karyotype group. There was no significant difference in response of AML patients received the standard "3+7 regimen" and pre-excitation chemotherapy in the treatment of normal and abnormal karyotype groups. The relapse free survival time (RFS) was longer in the normal karyotype group, but there was no significant difference in overall survival time (OS).@*CONCLUSION@#The abnormal karyotype of AML is an independent prognostic factor, monosomal karyotype shows a poor prognosis, and the recurrence rate in AML patients with monosomal karyotype is higher.

Differential Regulation of Bruton's Tyrosine Kinase by the Ubiquitin Pathway / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the regulation of Bruton's tyrosine kinase (Btk) and to explore its possible mechanism.</p><p><b>METHODS</b>After treatment with the proteasome inhibitors and/or phorbol esters (PMA), the mRNA and protein expression level of Btk was detected by RT-PCR and Western blot, respectively. The ubiquitination level of Btk in B lymphoblastoid A20 cells was estimated after stimulation via the crosslinking of BCR with anti-IgM antibody. The cotransfection of COS-7 cell with Btk, ubiquitin and Cbl was performed, then the ubiquitination level of Btk was measured. The Btk ubiquitination level was detected after ectopic expression of ubiquitin transfected with the wild type or triple mutant of Ub (K29R, K48R, K63R) . Mono-ubiquitination of Btk was detected with antibodies preferentially against monovalent ubiquitin; in addition, the protein expression levels of chloroquine-treated stably transfected cells expressing Btk-GFP were detected by Western blot, and quantified with the strength of GFP fluorescence.</p><p><b>RESULTS</b>In the presence of proteasome-specific inhibitors and/or PMA, steady-state levels of Btk protein were reduced due to decrease of transcription. Posttranslational modification of Btk by ubiquitination was observed, which was related with the level of Btk expression and activation. The E3 ubiquitin ligase Cbl, which binds to Btk, was also found to ubiquitinate this kinase. Altogether, the data of this study strongly suggest that Btk is regulated by poly- and/or mono-ubiquitination events.</p><p><b>CONCLUSION</b>The Btk protein is dictated by its expression level through the ubiquitination pathway.</p>