SDF-1α/CXCR4 Mediated Drug Resistance Can be Reversed by Ibrutinib in Acute Lymphoblastic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of Ibrutinib on the chemoresistance mediated by SDF-1α/CXCR4 axis in ALL cells.</p><p><b>METHODS</b>Flow cytometry was used to detect the apoptosis of cell line and expression of surface membrane CXCR4, Western blot was used to determine the expression level of CXCR4, ERK and Bcl-xL proteins, qPCR was used to assay the mRNA level of CXCR4.</p><p><b>RESULTS</b>Ibrutinib enhanced the apoptosis induced by adriamycin(ADR) (17.100±4.3% to 28.133±3.16%); Ibrutinib inhibited the phosphorylation of CXCR4 induced by SDF-1α and with concentration- and time- dependent manner (r=-0.99659, r=-0.99764, r=-0.99980). Ibrutinib inhibited the expression and activity of CXCR4 downstream signaling molecules pERK and BCL-xL.</p><p><b>CONCLUSION</b>Ibrutinib can enhance the sensitivity of SUP-B15 to ADR, reverse SDF-1α/CXCR4-mediated chemoresistance in Phacute lymphoblastic leukemia cells. This mechanism of ibrutinib may be assosiated with inhibiting CXCR4/ERK/BCL-xL.</p>

Expression of Btk and NFκB in Acute Lymphoblastic Leukemia Cells and Its Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the role of Btk and NFκB in the incidence, development, prognosis and therapeutic efficacy for acute lymphoblastic leukemia(ALL) through detecting their expression in leukemia cells.</p><p><b>METHODS</b>Bone marrow samples from 51 ALL patients were collected, and the mononuclear cells were separated by Ficoll density gradient centrifugation. The expressions of Btk and NFκB at RNA and protein levels were detected by RT-PCR and Western blot respectively.</p><p><b>RESULTS</b>(1)At protein level, Btk and NFκB were expressed in all newly diagnosed 51 ALL patients, among them 38 patients had higher expression level of Btk, 34 patients had high NFκB expression level. The expression of Btk and NFκB was higher in the cells from newly diagnosed ALL patients than that in the cells from patients in CR(P<0.05), and the expression of Btk and NFκB was higher in relapsed ALL patients. (2)The expression of Btk and NFκB in the ALL patients was followed-up higher expression of Btk: among the 38 newly diagnosed B-ALL cases, 27 experienced CR (71%) and 12 of which achieved CR after one course chemotherapy (one course CR) (31%). Moreover, 16 out of the 27 CR patients relapsed after a short period (less than 6 months) (59%). On the contrary, among the 13 patients with low Btk expression, 11 achieved CR (84.6%) after one course and 1 relapsed (8 months after CR) (7.6%). A similar pattern of NFκB expression was observed.</p><p><b>CONCLUSION</b>Btk and NFκ B may play an important role in the incidence and progression of ALL, possibly serving as the potential therapeutic targets of ALL and the indexes for prognosis.</p>

Influence of Co-inhibiting mTORC2 and HSP90 on Proliferation Apoptosis of Multiple Myeloma Cells / 中国实验血液学杂志

<p><b>UNLABELLED</b>Objective：To explore the influence of co-inhibiting mTORC2 and HSP90 on the proliferation and apoptosis of multiple myeloma(MM) cell line U266.</p><p><b>METHODS</b>During culture, the human MM cell line U266 were treated with 20 nmol/L of rapamycin, 600 nmol/L 17-AAG, 20 nmol/L of rapamycin + 600 nmol/L 17-AGG and phosphate-buffered saline (PBS), then the growth inhibition rate, morphologic changes, apoptosis rate and the expression of caspase 3 and ATK protein in U266 cells were compared and analyzed.</p><p><b>RESULTS</b>The rapamycin and 17-AAG both could inhibit the growth of U266 cells, while the inhibitory effect of rapamycin in combination with 17-AAG on growth of U266 cells was significantly higher them that of rapamycin and 17-AAG alone and control (PBS); the apoptosis rate of U266 cells treated with rapamycin, 17-AAG and their combination was higher than that of control PBS groups, and the efficacy of 2 drug conbination was higher than that of control PBS group, and the efficacy of 2 drug combination was superior to single drug. The expression levels of caspase 3 and ATK in U266 cells treated with rapamycin, 17-AAG and their combination were higher and lower than those in control group respectively, and the efficacy of 2 drug combination was superior to signle drug. There were significant difference between them (P<0.05).</p><p><b>CONCLUSION</b>The co-inhibition of mTORC2 and HSP90 can suppress the proliferation and induce the apoptosis of MM cells.</p>

Research advance of p53 gene in mantle cell lymphoma / 中国实验血液学杂志

Mantle cell lymphoma(MCL) is an independent uncommon subtype of B-cell non-Hodgkin's lymphoma (NHL) according to World Health Organization classification of hematopoietic and lymphoid tissue tumors. The genetic hallmark of MCL is the chromosomal translocation t(11;14)(q13;q32) that leads to upregulation of cyclin D1, an important regulator of the G(1) phase in the cell cycle. This genetic aberration is virtually present in all cases of MCL. It is characterized by distinct clinical features and outcome which is affected by a series of additional genetic aberration including the genomic guardian-P53 gene. This article reviews the effects of P53 gene aberrations including P53 deletion, mutation and their mutual relationship in MCL, and novel therapeutic regimens for MCL patients with P53 aberrations.