ABSTRACT
<p><b>OBJECTIVE</b>To explore the role of heterogeneous nuclear ribonucleoprotein(hnRNP) K regulating autophagy in the drug resistance of acute myeloid leukemia, so as to provide a new molecular marker for treatment of leukemia.</p><p><b>METHODS</b>The relationship between the expression level of hnRNP K and the drug resistance of myeloid leukemia was verified by fluorescence quantitative PCR; the expression of autophagy related protein LC3I/ II was detected by Western blot after the hnRNP K was modulated by RNA interference technology; the sensitivity of leukemia cells to doxorubicin was analyzed before and after the expression of hnRNP K were modulatd.</p><p><b>RESULTS</b>The expression of hnRNP K and LC3I/II significantly increased in bone marrow nonremission patients and in drug resistant cell line, however, the expression of LC3I/ II decreased when the expression of hnRNP K were reduced, while the sensitivity of cells to adriamycin could be recovered.</p><p><b>CONCLUSION</b>hnRNP K may be involved in the formation of adriamycin resistance in acute myeloid leukemia by regulating autophagy.</p>
ABSTRACT
This study was aimed to explore the progression mechanism of chronic myeloid leukemia, so as to provide the new molecular markers for evaluation of CML clinical outcome and selection of treatment. The microarray data of genes related with progression from different phase of chronic myeloid leukemia (CML) were collected from public data depository GEO (Gene expression datasets). SAM analysis, fold change filtering, cross comparison were used to analyze the data and identify different genes. Moreover, MeV and pSTIING sofewares were used to analyze the key differential genes and signal pathways. At last, Q-PCR were used to confirm the predicted key gene. The results indicated that after comparison, 9 genes were differentially expressed from AP to BC, and the integrin-mediated cell adhesion , focal adhesion, regulation of actin cytoskeleton were the principal pathways during CML progression. Network construction analysis found that AP-related genes or pathways may be the original signals; and MLLT4, WDR35 and EPHB4 were the key genes for CML progression. EPHB4 was confirmed by Q-PCR in CML BC patients and CP patients. It is concluded that MLLT4, WDR35, EPHB4, integrin-mediated cell adhesion, focal adhesion and regulation of actin cytoskeleton are the principal genes and pathways during CML progression.