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

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

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.

RESEARCH ARTICLE Open Access Investigating clinical characteristics and prognostic factors in patients with chronic osteomyelitis of humerus

Background:Chronic osteomyelitis in the humerus,which has complex neuroanatomy and a good soft tissue envelope,represents a unique clinical challenge.However,there are relatively few related studies in the literature.This article retrospectively reviewed a large case series with the aims of sharing our management experiences and further determining factors associated with the outcomes.Methods:Twenty-eight consecutive adult patients with a mean age of 36 years were identified by reviewing the osteomyelitis database of our clinic centre.The database was used to prospectively identify all osteomyelitis cases between 2013 and 2017,and all data then was retrospectively analysed.Results:The mean follow-up period was 35 months(range 24–60).The aetiology was trauma in 43%(12)of the patients and haematogenous in 57%(16)of the patients,and Staphylococcus aureus was a solitary agent in 50%(14)of the patients.Host-type(Cierny’s classification)was IA in 8,IIIB in 11 and IVB in 9 patients.All patients required debridement followed by the placement of a temporary antibiotic-impregnated cement spacer(rod).Seventeen patients received a cement-coated plate for internal fixation after debridement,and 13 patients needed bone grafts when the spacer was staged removed.All patients attained an infection-free bone healing state at the final follow-up.The final average DASH(disabilities of the arm,shoulder and hand)score was 18.14±5.39,while 6 patients(two developed traumatic olecranarthritis,four developed radial nerve injuries)showed the lowest levels of limb function(p=0.000)and were unemployed.Three patients(type I;significant difference between type I versus type III and type IV patients,p<0.05)experienced recurrence after debridement and underwent a second revision,which was not related to the bone graft(p=0.226)or plate fixation(p=0.050).Conclusions:Humeral chronic osteomyelitis can be treated with general surgery and anti-infective therapy;medullary(type I)infection presents a challenge,and the antibiotic-coated cement plate provides favourable fixation without increasing recurrence of infections.Clinicians should be aware of potential iatrogenic nerve injuries when treating these patients with complicated cases,and an experienced surgeon may improve the outcome.