Study on the Relationship between Integrin 2A and Drug Resistance in Chronic Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the expression pattern and clinical significance of Integral membrane protein 2A（ITM2A） in drug resistant patients with chronic myeloid leukemia (CML).@*METHODS@#The expression of ITM2A in CML was evaluated by qRT-PCR, Western blot and immunocytochemistry. In order to understand the possible biological effects of ITM2A, apoptosis, cell cycle and myeloid differentiation antigen expression of CML cells were detected by flow cytometry after over-expression of ITM2A. The nuderlying molecular mechanism of its biological effect was explored.@*RESULTS@#The expression of ITM2A in bone marrow of CML resistant patients was significantly lower than that of sensitive patients and healthy donors（P<0.05）. The CML resistant strain cell K562R was successfully constructed in vitro. The expression of ITM2A in the resistant strain was significantly lower than that in the sensitive strain(P<0.05). Overexpression of ITM2A in K562R cells increased the sensitivity of K562R cells to imatinib and blocked the cell cycle in G2 phase(P<0.05), but did not affect myeloid differentiation. Mechanistically, up-regulation of ITM2A reduced phosphorylation in ERK signaling (P<0.05).@*CONCLUSION@#The expression of ITM2A was low in patients with drug resistance of CML, and the low expression of ITM2A may be the key factor of imatinib resistance in CML.

Potential Value of Cancer-Associated Fibroblasts in Hematological Malignancies--Review / 中国实验血液学杂志

Cancer-associated fibroblasts (CAF), as one of the most important components of tumor microenvironment, which plays important role in tumorigenesis, development, infiltration and metastasis of cancers. In a variety of solid tumors, CAF can even determine the fate of tumor cells. In view of its pivotal role in promoting tumor progression, CAF has recently become a therapeutic target for a variety of tumors. However, there are a few studies on CAF in hematological malignancies. Recent studies have found that the resistance, relapse of AML, MM, CLL and myelofibrosis of MPN closely relate with CAF, so targeting CAF can effectively enhance the killing effect of chemotherapy drugs on tumor cells, thus improve the efficacy, CAF is expected to become a new target for the treatment of hematological malignancies. This review summarizes recent advances in cancer-associated fibroblasts in hematological malignancies.

Establishing the Ion Torrent PGM Sequencing Methods for the Clinical Diagnosis of MPN Patients / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the feasibility and relibility of rapidly and accurately acquiring the informations of gene mutations in MPN patients by using self-designed custom MPN mutation-related multipe-PCR primer kit and next generation Ion Torrent PGM sequencing platform.</p><p><b>METHODS</b>The bone marrow samples of 10 MPN patients with JAK2V617F and/or CALR, Phconfirmed by sanger sequencing method were collected and were re-detected by using next generation Ion Torrent PGM sequencing method, then the consistence of results of above-mentioned 2 kinds of detection methods was compared.</p><p><b>RESULTS</b>In terms of JAK2V617F, MPL and CALR mutations, the results of Ion Torrent PGM sequencing were complete consistent with results of Sanger sequencing, except 52 bp deletion of CALR gene, which conld not be detected by next generation Ion Torrent PGM sequencing method in all bone marrow samples.</p><p><b>CONCLUSION</b>The detection of multiple gene mutations in MPN patients by Ion Torrent PGM sequencing platform is feasible and can meet the needs of clinical testing. This method can complete detection of all 23 mutetions within 1-2 days, moreover, possesses advantages of high sensitivity, specificity, rapidity, high throughput and low cost.</p>