The impact of a vaccine mandate and the COVID-19 pandemic on influenza vaccination uptake in Western Australian health care students.

Annual influenza vaccination of health care students and workers helps protect themselves and patients from influenza, which has a high disease burden during seasonal peaks in Australia. Health care students are an important cohort whose early attitudes and habits towards influenza vaccination may influence future behaviours. We explored the knowledge, attitudes, and behaviours towards influenza vaccination of health care students in two universities from 2018 to 2020 using convergent mixed methodology. We also assessed the impact of two external events - the introduction of mandatory influenza vaccination for select students in 2019, and the COVID-19 pandemic in 2020. We found a significant increase in self-reported vaccination uptake between 2018 (73.5%) and 2020 (89.6%), with the mandate and COVID-19 pandemic being likely drivers of increased uptake. Vaccine mandates are effective but must be supported by easy accessibility, adequately addressing concerns around effectiveness and safety, and promotion of voluntary acceptance and trust.

Pulmonary ischaemia without pulmonary arterial thrombus in COVID-19 patients receiving extracorporeal membrane oxygenation: a cohort study.

AIM: To evaluate the incidence of pulmonary ischaemia in COVID-19 patients on extracorporeal membrane oxygenation (ECMO), and its correlation with pulmonary artery thrombosis. MATERIALS AND METHODS: Computed tomography (CT) thorax of all patients receiving ECMO with proven COVID-19 pneumonitis between March and May 2020 were analysed for the presence and extension of pulmonary thromboembolic disease. RESULTS: Fifty-one patients were reviewed. The mean (range) age of 45 (26-66) years; 38/51 (74.5%) were men. All patients had severe COVID-19 pneumonitis, and 18/51 (35.3%) had macroscopic thrombosis (15 with associated ischaemia); however, 13/51 (25.5%) patients had ischaemia without associated thrombus. CONCLUSION: The majority of patients with COVID-19 who received ECMO had areas of ischaemia within consolidated lungs, almost half of these without subtending pulmonary artery thrombosis. Although the prognostic significance of these findings is unclear, they are highly suggestive of lung ischaemia due to isolated microvascular immune thrombosis.

Awareness of fertility preservation among Chinese medical students.

INTRODUCTION: The fertility preservation (FP) services offered in Hong Kong are underutilised. There have been no previous studies on Chinese medical students to investigate the underlying reasons for this underutilisation in terms of awareness, knowledge, and attitudes towards FP and age-related fertility. METHODS: This was a cross-sectional survey among Chinese medical students in Hong Kong. RESULTS: The majority of participants (77.8%) were not familiar with any clinics or specialists who provide FP services. The vast majority (88.1%) underestimated female infertility at age 45 years, and 89.8% overestimated the age of male fertility decline. The students' FP knowledge was mainly acquired from electronic media (58.4%) and medical school (57.6%). Medical students showed overwhelming support towards FP for medical reasons (97.9%) but had mixed responses about FP for elective reasons related to career development in women (58.8%). Of the participants, 80.2% agreed that the government should subsidise FP services for patients with medical reasons. CONCLUSION: This study highlights the limited awareness and knowledge of FP among Chinese medical students. There is a strong worldwide need to increase education about and exposure to FP in the medical curriculum and improve medical students' knowledge.

Psoas muscle atrophy following unilateral hip arthroplasty.

BACKGROUND: Studies have demonstrated the presence of muscle atrophy around the hip in patients with hip osteoarthritis. Few studies have examined the psoas muscle or assessed it at a paraspinal level in patients post-total hip arthroplasty. The aim of this study was to determine if there is significant psoas muscle atrophy as indicated by muscle cross-sectional area and high degree of fat infiltration post-unilateral hip arthroplasty. METHODS: Retrospective analysis of 341 patients with unilateral hip implant and subsequent lumbar spine MRI over a 8-year period was performed. Fat infiltration and cross-sectional area of the psoas muscle at L3/4 level were measured by two musculoskeletal fellows (1 year experience in musculoskeletal radiology), and comparison made between the implant and non-operative sides was made. Fat infiltration was measured using the modified Goutallier grading. The degree of hip osteoarthritis in the non-operative side was measured using the Kellgren-Lawrence grading. The data was analysed using paired t test, ANOVA, unpaired t test, Pearson correlation and Jonckheere-Terpstra test. RESULTS: The cross-sectional area of the psoas muscle on the implant side was significantly less than the non-operative side. There was significance between the cross-sectional area difference and the fat grade of the implant side. CONCLUSION: Our results demonstrate psoas atrophy on the implant side compared to the non-operative side in post-unilateral implant patients. Post-operative hip implant rehabilitation may benefit from more focused psoas strengthening exercises to improve functional outcome.

Ex vivo interaction between blood components and hormone-dependent breast cancer cells induces alterations associated with epithelial-mesenchymal transition and thrombosis.

The prevalence of breast cancer is steadily increasing with metastasis and thromboembolic complications identified as the most common causes of death. The acquisition of an aggressive phenotype by hormone-dependent breast cancers is mediated by Transforming Growth Factor Beta 1 (TGF-ß1) expression and is associated with epithelial-mesenchymal transition (EMT) and, potentially, increased propensity for thrombosis. We investigated this phenomenon by assessing the effect of platelet-rich plasma (PRP) and whole blood (WB) on parameters of EMT and hypercoagulation in vitro. MCF-7 breast cancer cells were cultured under standard conditions, followed by co-culture with PRP or WB. Cells were processed for real-time PCR (TGF-ß1 and vimentin), electron microscopy or immunocytochemistry (TGF-ß1). Micrographs were qualitatively assessed, and real-time PCR data analyzed with PAST Statistical Software. The addition of blood components heightened TGF-ß1 immunolocalization and significantly increased corresponding gene expression. Both PRP and WB significantly increased vimentin expression and induced a shape change from a typical epithelial phenotype to a spindle-shape morphology, indicative of EMT. Fibrin fiber, network and plaque formation indicated a hypercoagulatory environment. The results thus show that in preparation for hematogenous metastasis, hormone-dependent breast cancer cells assume an aggressive phenotype associated with EMT, simultaneously increasing the propensity for the formation of thrombo-emboli.

Tumor inhibitory effects of intravesical Ganoderma lucidum instillation in the syngeneic orthotopic MB49/C57 bladder cancer mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (GL) has been traditionally used in oriental medicine as superior health tonic, and there are numerous scientific evidences of its antitumorigenic activities. AIM OF THE STUDY: To evaluate the intravesical chemopreventive effects of ethanol extract of GL (GLe) on bladder cancer. MATERIALS AND METHODS: Intravesical therapy is defined as the direct instillation of a liquid drug into bladder through a catheter. Bacille Calmette-Guerin(BCG) solution is applied intravesically as a conventional immunotherapy for preventing recurrence of bladder cancer. By adopting the MB49/C57 bladder cancer mice model, an overall 60 MB49-implanted mice were randomized into 3 groups and treated according to 3 treatment arms, including GLe, BCG and PBS. Additionally, wild-type mice without MB49 cell inoculation and treated with PBS were used as the negative control group. Testing agents were instilled intravesically for 2 h and repeated after one week for evaluating the effects on preventing the tumor formation and growth. The treated-mice were closely monitored for major adverse effects. RESULTS: GLe demonstrated more potent cytotoxic effects than BCG on MB49 cells, although both in dose-dependent manner. In the MB49-implanted mice, 80 µg/ml GLe was shown to delay the tumor formation by one week, whereas the averaged tumor volume measured at endpoint was 3.6-fold and 4.6-fold smaller than that of the BCG or PBS, respectively. However, no significant effects were observed on body weight and hematuria. CONCLUSION: Current findings in mice suggested intravesical GLe therapy as an effective and safe chemopreventive strategy for inhibiting bladder tumor formation.

Long-term impact of childhood hepatitis B vaccination programs on prevalence among Aboriginal and non-Aboriginal women giving birth in Western Australia.

BACKGROUND/AIMS: To evaluate the long-term effect of infant and childhood hepatitis B (HBV) vaccination programs among birthing women in Western Australia. METHODS: A cohort of Western Australian women born from 1974 to 1995 was created using Birth Registrations and Electoral Roll records. They were linked to a perinatal register and notifiable diseases register to identify women having respectively their first births between 2000 and 2012 and diagnoses of HBV infections. HBV prevalence was estimated in Aboriginal and non-Aboriginal women, and according to maternal birth year cohorts. RESULTS: Of 66,073 women, 155 (0.23%) had a linked non-acute HBV notification. HBV prevalence was five times higher in Aboriginal women compared to their non-Aboriginal counterparts (0.92%, 95%CI 0.65-1.18 versus 0.18%, 0.15-0.21). Among Aboriginal women, after adjusting for year of giving birth and region of residence, those born in the targeted infant and school-based vaccination era (maternal year of birth 1988-1995) had an 89% lower risk (adjusted odds ratio [aOR] 0.11, 0.04-0.33) of HBV than those born in the pre-vaccination era (1974-1981). Prevalence also differed between Aboriginal women residing in rural/remote areas compared to those in major cities (aOR 3.06, 1.36-6.88). Among non-Aboriginal women, no significant difference in HBV prevalence was observed by maternal birth cohort (p = 0.20) nor by residence (p = 0.23), but there were significant differences by ethnicity with a 36-fold higher prevalence (aOR 36.08, 22.66-57.46) in non-Caucasian versus Caucasian women. CONCLUSIONS: A significant decline in HBV prevalence in Aboriginal birthing mothers was observed following the introduction of HBV vaccination programs in Western Australia. There were also considerable disparities in prevalence between women by area of residence and ethnicity. Our findings reflect those observed in women in other Australian jurisdictions. Continued surveillance of HBV prevalence in birthing mothers will provide ongoing estimates of HBV vaccination program impact across Australia and the populations most at risk of chronic HBV.

Combined inhibition of ß-catenin and Bcr-Abl synergistically targets tyrosine kinase inhibitor-resistant blast crisis chronic myeloid leukemia blasts and progenitors in vitro and in vivo.

Tyrosine kinase inhibitor (TKI) resistance and progression to blast crisis (BC), both related to persistent ß-catenin activation, remain formidable challenges for chronic myeloid leukemia (CML). We observed overexpression of ß-catenin in BC-CML stem/progenitor cells, particularly in granulocyte-macrophage progenitors, and highest among a novel CD34+CD38+CD123hiTim-3hi subset as determined by CyTOF analysis. Co-culture with mesenchymal stromal cells (MSCs) induced the expression of ß-catenin and its target CD44 in CML cells. A novel Wnt/ß-catenin signaling modulator, C82, and nilotinib synergistically killed KBM5T315I and TKI-resistant primary BC-CML cells with or without BCR-ABL kinase mutations even under leukemia/MSC co-culture conditions. Silencing of ß-catenin by short interfering RNA restored sensitivity of primary BCR-ABLT315I/E255V BC-CML cells to nilotinib. Combining the C82 pro-drug, PRI-724, with nilotinib significantly prolonged the survival of NOD/SCID/IL2Rγ null mice injected with primary BCR-ABLT315I/E255V BC-CML cells. The combined treatment selectively targeted CML progenitors and inhibited CD44, c-Myc, survivin, p-CRKL and p-STAT5 expression. In addition, pretreating primary BC-CML cells with C82, or the combination, but not with nilotinib alone, significantly impaired their engraftment potential in NOD/SCID/IL2Rγ-null-3/GM/SF mice and significantly prolonged survival. Our data suggest potential benefit of concomitant ß-catenin and Bcr-Abl inhibition to prevent or overcome Bcr-Abl kinase-dependent or -independent TKI resistance in BC-CML.

The benefits of newborn screening for cystic fibrosis: The Canadian experience.

BACKGROUND: The impact of newborn screening (NBS) for cystic fibrosis (CF) on early indicators of long-term health was evaluated in the context of government-sponsored healthcare and access to current therapies. METHODS: Using data from the Canadian CF Registry between 2008 and 2013, we compared the rates of respiratory infections and markers of nutritional status in those diagnosed through NBS to those who were diagnosed clinically within the same time period using Mann-Whitney and Fischer's exact test as appropriate. RESULTS: The study included 303 subjects, 201 in the NBS group and 102 in the non-NBS group. NBS patients were diagnosed earlier and had their first clinic visit at a younger age. Pancreatic insufficiency was less common in NBS patients. The incidence of Pseudomonas aeruginosa and Staphylococcus aureus were lower in NBS patients. After adjusting for age at clinic visit, gender, pancreatic status, and Pseudomonas aeruginosa infection status, mean z-scores for weight-for-age and height-for-age were higher in NBS patients, with no differences in BMI-for-age. CONCLUSIONS: NBS programs for CF lead to improved long-term health outcomes for the CF population.

Electromagnetic waves in a model with Chern-Simons potential.

We investigated the appearance of Chern-Simons terms in electrodynamics at the surface or interface of materials. The requirement of locality, gauge invariance, and renormalizability in this model is imposed. Scattering and reflection of electromagnetic waves in three different homogeneous layers of media is determined. Snell's law is preserved. However, the transmission and reflection coefficient depend on the strength of the Chern-Simons interaction (connected with Hall conductance), and parallel and perpendicular components are mixed.

Comparison of text-messaging to voice telephone interviews for active surveillance of adverse events following immunisation.

OBJECTIVES: In 2013, the Follow-up and Active Surveillance of Trivalent Influenza Vaccine in Mums (FASTMum) program began using short message service (SMS) to collect adverse event information in pregnant women who recently received trivalent influenza vaccine (TIV). This study was designed to compare data collected via SMS and telephone for the purposes of monitoring vaccine safety. METHODS: A number of 344 women who received TIV were randomly assigned to a telephone interview group. They were telephoned seven days post-vaccination and administered a standard survey soliciting any adverse events following immunisation (AEFI) they experienced. They were matched by brand of vaccine, age group, and residence to 344 women who were sent a SMS seven days post-vaccination. The SMS solicited similar information. AEFI reported by SMS and telephone interview were compared by calculating risk ratios. RESULTS: Response rate was higher to SMS compared to telephone interview (90.1% vs. 63.9%). Women who were surveyed by SMS were significantly less likely to report an AEFI compared to women who were surveyed by telephone (RR: 0.41; 95% CI: 0.29-0.59). The greatest discrepancies between SMS and telephone interview were for self-reported injection site reactions (3.1% vs. 16.8%) and unsolicited (or "other") events (11.4% vs. 4.1%). Data collected by SMS was significantly timelier. CONCLUSIONS: Data collection by SMS results in significantly improved response rates and timeliness of vaccine safety data. Systems which incorporate SMS could be used to more rapidly detect safety signals and promote more rapid public health response to vaccine quality issues.

A fuzzy probabilistic method for medical diagnosis.

The max-min composition in fuzzy set theory has attained reasonable success in medical diagnosis in the past thirty years for estimating the probability of a patient diagnosed with a certain disease. However, there has been no theoretical justification why the method would work. We create a theoretical model to calculate the probabilities of hypothetical patients having designated diseases, and use simulated dataset to explain why the max-min composition has been successful. In addition, based on the theoretical model, we propose a fuzzy probabilistic method to estimate the probability of a patient having a certain disease. The proposed method may produce a more accurate estimate than the max-min composition.

Control of type 2 diabetes after 1 year of laparoscopic adjustable gastric banding in the helping evaluate reduction in obesity (HERO) study.

AIMS: The 5-year, open-label, prospective, observational helping evaluate reduction in obesity (HERO) study (N = 1106) examines efficacy and safety of the LAP-BAND AP(®) laparoscopic adjustable gastric band (LAGB) in obese patients. This interim analysis assessed the control of type 2 diabetes (T2D), 1 year after the implantation of the LAGB. METHODS: Baseline T2D was defined by chart review or use of antidiabetic medications or haemoglobin A1c (HbA1c) ≥ 7.0%. Control of T2D at 1 year was defined as A1c <7.0% (with or without antidiabetic medications). RESULTS: After 1 year, 187 of 273 patients with T2D at baseline had adequate data available to assess T2D status, of which 135 patients (72.2%) achieved target control of T2D compared with 42.8% control rate at baseline. Independent predictors of achieving target control at 1 year included the following: (i) shorter diabetes duration odds ratio (OR) 0.914 [95% confidence interval (CI), 0.839, 0.995, p = 0.038], (ii) not using insulin therapy OR 0.16 (95% CI, 0.06, 0.47, p < 0.001) and (iii) greater mean % weight loss OR 1.176 (95% CI, 1.093, 1.266, p < 0.001). Patients using insulin at baseline were 84% less likely to achieve control of T2D after 1 year; each additional year of diabetes at baseline reduced the likelihood of good control by 9%; and each 1% of weight loss increases the likelihood of good control by 18%. Rates of device-related adverse events and reoperations were low and were not significantly different between patients with and without baseline T2D at 1 year. CONCLUSIONS: Greater % weight loss, not using insulin therapy, and shorter disease duration predicted increased likelihood of target control of T2D, 1 year after implantation of the LAGB.

Apoptosis repressor with caspase recruitment domain is regulated by MAPK/PI3K and confers drug resistance and survival advantage to AML.

The apoptosis repressor with caspase recruitment domain (ARC) protein is known to suppress both intrinsic and extrinsic apoptosis. We previously reported that ARC expression is a strong, independent adverse prognostic factor in acute myeloid leukemia (AML). Here, we investigated the regulation and role of ARC in AML. ARC expression is upregulated in AML cells co-cultured with bone marrow-derived mesenchymal stromal cells (MSCs) and suppressed by inhibition of MAPK and PI3K signaling. AML patient samples with RAS mutations (N = 64) expressed significantly higher levels of ARC than samples without RAS mutations (N = 371) (P = 0.016). ARC overexpression protected and ARC knockdown sensitized AML cells to cytarabine and to agents that selectively induce intrinsic (ABT-737) or extrinsic (TNF-related apoptosis inducing ligand) apoptosis. NOD-SCID mice harboring ARC-overexpressing KG-1 cells had significantly shorter survival than mice injected with control cells (median 84 vs 111 days) and significantly fewer leukemia cells were present when NOD/SCID IL2Rγ null mice were injected with ARC knockdown as compared to control Molm13 cells (P = 0.005 and 0.03 at 2 and 3 weeks, respectively). Together, these findings demonstrate that MSCs regulate ARC in AML through activation of MAPK and PI3K signaling pathways. ARC confers drug resistance and survival advantage to AML in vitro and in vivo, suggesting ARC as a novel target in AML therapy.

Bilateral hand-assisted laparoscopic nephrectomy in adult polycystic kidney disease patients: a UK centre experience.

PURPOSE: We report our experience with bilateral hand-assisted laparoscopic nephrectomy in patients with adult polycystic kidney disease. MATERIALS & METHODS: Between November 2009 and November 2010, 3 patients with adult polycystic kidney disease underwent bilateral hand-assisted laparoscopic nephrectomy in our institution. Indications for bilateral nephrectomy included recurrent cyst hemorrhage, impaired gastrointestinal function and early satiety due to direct intestinal compression by large polycystic kidneys, and anatomical lack of space for future renal transplantation. We retrospectively reviewed the records of these patients and we are reporting our experience. RESULTS: All three patients successfully underwent bilateral hand-assisted laparoscopic nephrectomy with a mean operating time of 208 minutes (range 195 to 220). There were no conversions to open procedure. Blood loss was less than 100 ml in all cases. Mean renal unit size was of 2037 g (range 1798 to 2214). Hospital stay ranged from 10 to 12 days. One patient developed a chest infection postoperatively and suffered from a prolonged ileus. Another patient developed a retroperitoneal hematoma, which was treated conservatively. CONCLUSIONS: Bilateral hand-assisted laparoscopic nephrectomy is a feasible and safe procedure in adult polycystic kidney disease patients, which has potential benefits of a shorter hospital stay and reduced morbidity and mortality in comparison to open procedure.

'I am absolutely shattered': the impact of chronic low back pain on Australian Aboriginal people.

BACKGROUND: Aboriginal people in Australia have been uniquely identified as less susceptible to chronic low back pain (CLBP) disability when compared to non-Aboriginal populations, reportedly due to cultural beliefs about pain. A qualitative, culturally secure research approach was used to explore this assumption. METHODS: In-depth interviews were undertaken with 32 Aboriginal men and women with CLBP in regional and remote areas of Western Australia. Interviews were conducted collaboratively with male and female Aboriginal co-investigators, and with the support of local Aboriginal community organizations. A primary focus was to investigate the impact of CLBP from the perspective of Aboriginal people living with the condition. RESULTS: The experience of CLBP was found to be multidimensional, impacting on activities of daily life, employment, sport and family participation, emotional and cultural well-being. CONCLUSIONS: Contrary to previous assumptions, CLBP is profoundly disabling for some Aboriginal people and a priority health concern. Issues of gender, cultural obligations and the emotional consequences of CLBP are important consideration for health care. These findings, and the contextual approach used to gain an in-depth understanding of CLBP, may be relevant to populations elsewhere.

MRx102, a triptolide derivative, has potent antileukemic activity in vitro and in a murine model of AML.

Triptolide, isolated from the herb Tripterygium wilfordii, has been shown to potently induce apoptosis in various malignant cells by inhibiting RNA synthesis and nuclear factor-κB activity. Previously, we showed that triptolide promotes apoptosis in acute myeloid leukemia (AML) cells via the mitochondria-mediated pathway, in part, by decreasing levels of the anti-apoptotic proteins XIAP and Mcl-1. MRx102 is a triptolide derivative, currently in preclinical development. Here we show that MRx102 potently promoted apoptosis in AML cell lines, with EC(50) values of 14.5±0.6 nM and 37.0±0.9 nM at 48 h for OCI-AML3 and MV4-11 cells, respectively. MRx102, at low nanomolar concentrations, also induced apoptosis in bulk, CD34(+) progenitor, and more importantly, CD34(+)CD38(-) stem/progenitor cells from AML patients, even when they were protected by coculture with bone marrow derived mesenchymal stromal cells. MRx102 decreased XIAP and Mcl-1 protein levels and inhibited RNA synthesis in OCI-AML3 cells. In vivo, MRx102 greatly decreased leukemia burden and increased survival time in non-obese diabetic/severe combined immunodeficiency mice harboring Ba/F3-ITD cells. Collectively, we demonstrated that MRx102 has potent antileukemic activity both in vitro and in vivo, has the potential to eliminate AML stem/progenitor cells and overcome microenvironmental protection of leukemic cells, and warrants clinical investigation.

Activation of apoptosis signaling eliminates CD34+ progenitor cells in blast crisis CML independent of response to tyrosine kinase inhibitors.

Despite being highly effective for newly diagnosed chronic myeloid leukemia (CML), imatinib not only is inactive against quiescent CML stem cells, but also has limited activity against blast crisis (BC) CML. The relative activity of Bcr-Abl and the expression levels of antiapoptotic proteins in proliferating and quiescent CD34(+) BC CML progenitor cells and the effects of targeting antiapoptotic proteins in these cells are unknown. Here we report higher levels of p-CrkL in quiescent than in proliferating CD34(+) progenitor cells and comparable expression levels of Bcl-2, Bcl-xL, Mcl-1 and XIAP in the two populations in BC CML. Inhibition of Bcl-2/Bcl-xL by ABT-737 in cells from patients with tyrosine kinase inhibitor (TKI)-resistant BC CML promoted apoptosis in quiescent CD34(+) progenitor cells with an efficacy similar to that in proliferating cells. Combination of ABT-737 with imatinib (which decreases Mcl-1 levels) or triptolide (which decreases Mcl-1 and XIAP) synergistically induced death of both proliferating and quiescent CD34(+) progenitor cells obtained from TKI-resistant BC CML patients. These results suggest that antiapoptotic proteins are critical targets in BC CML and that activation of apoptosis signaling can eliminate both proliferating and quiescent CD34(+) progenitor cells in BC CML, independent of response to TKIs.

MEK inhibition enhances ABT-737-induced leukemia cell apoptosis via prevention of ERK-activated MCL-1 induction and modulation of MCL-1/BIM complex.

Recently, strategies for acute myeloid leukemia (AML) therapy have been developed that target anti-apoptotic BCL2 family members using BH3-mimetic drugs such as ABT-737. Though effective against BCL2 and BCL-X(L), ABT-737 poorly inhibits MCL-1. Here we report that, unexpectedly, ABT-737 induces activation of the extracellular receptor activated kinase and induction of MCL-1 in AML cells. MEK inhibitors such as PD0325901 and CI-1040 have been used successfully to suppress MCL-1. We report that PD0325901 blocked ABT-737-induced MCL-1 expression, and when combined with ABT-737 resulted in potent synergistic killing of AML-derived cell lines, primary AML blast and CD34+38-123+ progenitor/stem cells. Finally, we tested the combination of ABT-737 and CI-1040 in a murine xenograft model using MOLM-13 human leukemia cells.Whereas control mice and CI-1040-treated mice exhibited progressive leukemia growth, ABT-737, and to a significantly greater extent, ABT-737+CI-1040 exerted major anti-leukemia activity. Collectively, results demonstrated unexpected anti-apoptotic interaction between the BCL2 family-targeted BH3-mimetic ABT-737 and mitogen-activated protein kinase signaling in AML cells: the BH3 mimetic is not only restrained in its activity by MCL-1, but also induces its expression. However, concomitant inhibition by BH3 mimetics and MEK inhibitors could abrogate this effect and may be developed into a novel and effective therapeutic strategy for patients with AML.