ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification / 医学前沿

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.

Abivertinib inhibits megakaryocyte differentiation and platelet biogenesis / 医学前沿

Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34+ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34+ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.

Clinical characteristics and prognostic values of 1p32.3 deletion detected through fluorescence in situ hybridization in patients with newly diagnosed multiple myeloma: a single-center study in China / 医学前沿

This study aimed to investigate the prevalence, clinical characteristics, and prognostic impact of 1p32.3 deletion in patients with newly diagnosed multiple myeloma (MM). A retrospective analysis was conducted on 411 patients with newly diagnosed MM; among which, 270 received bortezomib-based therapies, and 141 received thalidomide-based therapies. Fluorescence in situ hybridization (FISH) was performed to detect six cytogenetic abnormalities, namely, del(1p32.3), gain(1q21), del(17p13), del(13q14), t(4;14), and t(11;14). Results showed that 8.3% of patients with MM were detected with del(1p32.3) and had significantly more bone marrow plasma cells (P = 0.025), higher β2-microglobulin levels (P = 0.036), and higher lactate dehydrogenase levels (P = 0.042) than those without del(1p32.3). Univariate analysis showed that patients with del(1p32.3) under thalidomide-based therapies (median PFS 11.6 vs. 31.2 months, P = 0.002; median OS 16.8 vs. 45.9 months, P < 0.001) were strongly associated with short progression-free survival (PFS) (P = 0.002) and overall survival (OS) (P < 0.001). Multivariate analysis revealed that del(1p32.3) remained a powerful independent factor with worse PFS (P = 0.006) and OS (P = 0.016) for patients under thalidomide-based treatments. Patients with del(1p32.3) under bortezomib-based treatments tended to have short PFS and OS. In conclusion, del(1p32.3) is associated with short PFS and OS in patients with MM who received thalidomide- or bortezomib-based treatments.

The clinical efficacy of all-trans retinoic acid plus arsenic trioxide in 177 newly diagnosed acute promyelocytic leukemia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical efficacy of all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) in induction and maintenance therapy in newly diagnosed acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>A retrospective analysis of 298 newly diagnosed APL patients from the department of hematology, First Affiliated Hospital of Zhejiang University since September 2004 to December 2013, including 177 cases with ATRA plus ATO and 116 ATRA plus chemotherapy (CT), was performed to investigate the clinical efficacy between the low-intermediate (WBC≤10×10⁹/L) and high (WBC>10×10⁹/L) risk APL patients, respectively.</p><p><b>RESULTS</b>For the low-intermediate risk patients, the relapse rate in ATRA plus CT and ATRA plus ATO are 22.0% and 6.1% (P=0.004), respectively; the 3 years estimated relapse-free survival (RFS) are 78.0% and 92.9% (P=0.021), respectively. For the high risk patients, the relapse rate in ATRA plus CT and ATRA plus ATO are 25.0% and 5.2% (P=0.035), respectively; the 3 years estimated RFS rate were 80.8% and 93.0% (P=0.021), respectively. But the rate of early death (ED), complete remission (CR) and overall survival (OS) between the two therapy protocols had no statistical difference (P>0.05).</p><p><b>CONCLUSION</b>ATRA plus ATO in induction and maintenance therapy might prolong the RFS time of the low-intermediate risk APL patients and decrease the relapse rate of the low, intermediate and high risk APL patients.</p>

Anti-fatigue effects of polysaccharides extracted from Rhodiolae Radix.

The purpose of the present study was to determine the effects of polysaccharide from Rhodiolae Radix (PRR) on physical fatigue using a forced swimming test in male mice. 96 mice were divided randomly into four groups based on body weight (n = 24). One of the groups was the control group; the others were PRR supplemented groups (25, 50 and 100 mg/kg body weight). Forced swimming test of mice were carried out after 28 days of PRR administration, and the blood lactic acid (BLA), blood urea nitrogen (BUN), liver glycogen and muscle glycogen contents were deter-mined. The data suggest that PRR can extend the exhaustive swimming time of the mice, as well as increase the tissue glycogen contents, and decrease the BLA and BUN contents. These results indicated that PRR had significant anti-fatigue effects.

THE PROTECTIVE EFFECT OF BERBAMINE ON CEREBRAL INFARCTION MODEL IN RATS / 中国药理学通报

The cerebral infarction model was made according to Chen et al To evaluate the severity of infarction the quantity of Evan's blue was measured. The cerebral infarction size was determined by TTC stain. The results showed that ligating the right common carotid artery and the right middle cerebal artery and clamping the left common carotid artery could induce cerebral cortex in farction. Berbamine could decreased the level of Evan's blue and reduce the infarction size compared with control group. It suggests that berbamine possesses protective effect on experimental induced cerebral infarction.