• Asian Pacific Journal of Cancer Prevention
• /
• 제16권15호
• /
• pp.6627-6632
• /
• 2015

Background: We conducted a study exploring the clinical safety and efficacy of decitabine in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), combined with a complex karyotype. Materials and Methods: From April 2009 to September 2013, a total of 35 patients with AML/MDS combined with a complex karyotype diagnosed in the First Affiliated Hospital of Soochow University were included for retrospective analysis. All patients were treated with decitabine alone ($20mg/m^2$ daily for 5 days) or combination AAG chemotherapy (Acla 20mg qod*4d, Ara-C $10mg/m^2$ q12h*7d, G-CSF $300{\mu}g$ qd, the dose of G-CSF adjusted to the amount in blood routinely). Results: In 35 patients, 15 exhibited a complete response (CR), and 6 a partial response (PR), the overall response rate (CR+PR) being 60% (21 of 35). Median disease-free survival was 18 months and overall survival was 14 months. In the 15 MDS patients with a complex karyotype, the CR rate was 53.3% (8 of 15); in 20 AML patients with complex karyotype, the overall response rate was 65% (13 of 20). The response rate of decitabine alone (22 cases) was 56.5% (13 of 22), while in the combination chemotherapy group (13 cases), the effective rate was 61.5% (8 of 13)(P>0.05). There are 15 patients with chromosome 7 aberration, after treatment with decitabine, 7 CR, 3 PR, overall response rate was 66.7% (10 of 15). Of 18 patients with 3 to 5 kinds of chromosomal abnormalities, 66.7% demonstrated a response; of 17 with more than 5 chromosomal abnormalities, 52.9% had a response. In the total of 35 patients, with one course (23 patients) and ${\geq}$two courses (12 patients), the overall response rate was 40.9% and 92.3% (P<0.05). Grade III to IV hematological toxicity was observed in 27 cases (75%). Grade III to IV infections were clinically documented in 7 (20%). Grades I to II non-hematological toxicity were infections (18 patients), haematuria (2 patients), and bleeding (3 patients). With follow-up until September 2013, 7 patients were surviving, 18 had died and 10 were lost to follow-up. In the 6 cases who underwent allogeneic hematopoietic stem cell transplantation (HSCT) all were still relapse-free survivors. Conclusions: Decitabine alone or combination with AAG can improve outcome of AML/MDS with a complex karyotype, there being no significant difference decitabine in inducing remission rates in patients with different karyotype. Increasing the number of courses can improve efficiency. This approach with fewer treatment side effects in patients with a better tolerance should be employed in order to create an improved subsequent chance for HSCT.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권12호
• /
• pp.7719-7724
• /
• 2013

Background: Overexpression of survivin, a known inhibitor of apoptosis, is associated with tumor progression and drug resistance in numerous malignancies, including leukemias. The aim of this study was to investigate the effect of a specific survivin small interference RNA (siRNA) on proliferation and the sensitivity of HL-60 acute myeloid leukemia (AML) cells to the chemotherapeutic drug etoposide. Materials and Methods: The cells were transfected with siRNAs using Lipofectamine $^{TM}2000$ transfection reagent. Relative survivin mRNA and protein levels were measured by quantitative real-time PCR and Western blotting, respectively. Trypan blue exclusion assays were performed to monitor tumor cell proliferation after siRNA transfection. The cytotoxic effects of etoposide and survivin siRNA, alone and in combination, on leukemic cells were determined using MTT assay. Apoptosis was assessed by ELISA cell death assay. Results: Survivin siRNA markedly reduced both mRNA and protein expression levels in a time-dependent manner, leading to distinct inhibition of cell proliferation and increased spontaneous apoptosis. Surprisingly, survivin siRNA synergistically increased the cell toxic effects of etoposide. Moreover, survivin down-regulation significantly enhanced its induction of apoptosis. Conclusions: Our study suggests that down-regulation of survivin by siRNA can trigger apoptosis and overcome drug resistance of leukemia cells. Therefore, survivin siRNA may be an effective adjuvant in AML chemotherapy.

• BMB Reports
• /
• 제48권8호
• /
• pp.427-428
• /
• 2015

Despite high interests on microenvironmental regulation of leukemic cells, little is known for bone marrow (BM) niche in leukemia patients. Our recent study on BMs of acute myeloid leukemia (AML) patients showed that the mesenchymal stromal cells (MSCs) are altered during leukemic conditions in a clinical course-dependent manner. Leukemic blasts caused reprogramming of transcriptomes in MSCs and remodeling of niche cross-talk, selectively suppressing normal primitive hematopoietic cells while supporting leukemogenesis and chemo-resistance. Notably, differences in BM stromal remodeling were correlated to heterogeneity in subsequent clinical courses of AML, i.e., low numbers of mesenchymal progenitors at initial diagnosis were correlated to complete remission for 5-8 years, and high contents of mesenchymal progenitor or MSCs correlated to early or late relapse, respectively. Thus, stromal remodeling by leukemic cell is an intrinsic part of leukemogenesis that can contribute to the clonal dominance of leukemic cells over normal hematopoietic cells, and can serve as a biomarker for prediction of prognosis. [BMB Reports 2015; 48(8): 427-428]

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권9호
• /
• pp.3941-3944
• /
• 2015

Background: Aberrant expression of HOX gene expression has been observed in cancer. The purpose of this study was to investigate the alteration of HOXA5 and HOXA9 expression and their clinical significance in acute meloid leukemia (AML). Materials and Methods: The expression of HOXA5 and HOXA9 genes of bone marrow samples from 75 newly diagnosed AML patients and 22 healthy controls for comparison were examined by Real-time quantitative PCR (RQ-PCR) assay. Statistical analysis was conducted to evaluate HOXA5 and HOXA9 expression as possible biomarkers for AML. Results: The results showed that the complete remission rate (52.6%) of the patients who highly expressed HOXA5 and HOXA9 was significantly lower than that (88.9%) in patients who lowly express the genes (P=0.015). Spearmann correlation coefficients indicated that the expression levels for HOXA5 and HOXA9 genes were highly interrelated (r=0.657, P<0.001). Meanwhile, we detected significant correlations between HOXA9 expression and age in this limited set of patients (P=0.009). Conclusions: The results suggest a prognostic impact of increased expression of HOXA5 and HOXA9 in AML patients.

• Clinical and Experimental Pediatrics
• /
• 제57권10호
• /
• pp.434-439
• /
• 2014

Treatment outcomes of pediatric cancers have improved greatly with the development of improved treatment protocols, new drugs, and better supportive measures, resulting in overall survival rates greater than 70%. Survival rates are highest in acute lymphoblastic leukemia, reaching more than 90%, owing to risk-based treatment through multicenter clinical trials and protocols developed to prevent central nervous system relapse and testicular relapse in boys. New drugs including clofarabine and nelarabine are currently being evaluated in clinical trials, and other targeted agents are continuously being developed. Chimeric antigen receptor-modified T cells are now attracting interest for the treatment of recurrent or refractory disease. Stem cell transplantation is still the most effective treatment for pediatric acute myeloid leukemia (AML). However, in order to reduce treatment-related death after stem cell transplantation, there is need for improved treatments. New drugs and targeted agents are also needed for improved outcome of AML. Surgery and radiation therapy have been the mainstay for brain tumor treatment. However, chemotherapy is becoming more important for patients who are not eligible for radiotherapy owing to age. Stem cell transplant as a means of high dose chemotherapy and stem cell rescue is a new treatment modality and is often repeated for improved survival. Drugs such as temozolomide are new chemotherapeutic options. In order to achieve 100% cure in children with pediatric cancer, every possible treatment modality and effort should be considered.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권4호
• /
• pp.2525-2528
• /
• 2013

The Homer protein family, also known as the family of cytoplasmic scaffolding proteins, which include three subtypes (Homer1, Homer2, Homer3). Homer3 can regulate transcription and play a very important role in the differentiation and development for some tissues (e.g. muscle and nervous systems). The current studies showed that Homer3 abnormal expression changes in acute myeloid leukemia (AML). Forced expression of Homer3 in transfected K562 cells inhibited proliferation, influenced the cell cycle profile, affected apoptosis induced by $As_2O_3$ through inhibition of Bcl2 expression, and also promoted cell differentiation induced by 12-O-tetra decanoylphorbol-acetate (TPA). These results showed that Homer3 is a novel gene which plays a certain role in the occurrence and development of AML.

• Investigative Magnetic Resonance Imaging
• /
• 제14권1호
• /
• pp.74-77
• /
• 2010

과립세포육종은 골수성 백혈병의 발현 형태의 하나로써, 과립세포들의 원시 전구체가 골수가 아닌 연조직에 침착하여 생긴 고형 종괴를 지칭한다. 저자들은 다른 전신 증상 없이 양쪽 안구의 돌출을 주소로 내원하여 광범위한 양쪽 안와-부비동 과립세포육종으로 진단된 22개월 남아의 CT 및 MR 소견을 보고한다. 종괴는 양측 안와 외하벽을 침범하여 양쪽 안구를 돌출시켰으며, 부비동, 상악골, 측두골, 광대뼈, 나비뼈, 벌집뼈, 입천장뼈를 포함한 거의 모든 머리뼈바닥의 골수에 침윤하고 주변에 연부 조직 종괴를 형성하였고, 해면정맥동의 아래 1/2을 침범하고 측두골 안쪽의 경질막이 비후된 소견을 동반하였다. 환아는 골수를 이용한 염색체 검사를 통해 8번과 21번 염색체의 상호전좌 t(8;21) (q22;q22)를 동반한 급성 골수성 백혈병으로 진단되었다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권10호
• /
• pp.4353-4358
• /
• 2014

Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.

• Biomolecules & Therapeutics
• /
• 제22권2호
• /
• pp.114-121
• /
• 2014

Refractoriness of acute myeloid leukemia (AML) cells to chemotherapeutics represents a major clinical barrier. Suicide gene therapy for cancer has been attractive but with limited clinical efficacy. In this study, we investigated the potential application of herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) based system to inhibit chemoresistant AML cells. We first generated Ara-C resistant K562 cells and doxorubicin-resistant THP-1 cells. We found that the HSV-TK/GCV anticancer system suppressed drug resistant leukemic cells in culture. Chemoresistant AML cell lines displayed similar sensitivity to HSV-TK/GCV. Moreover, HSV-TK/GCV killing of leukemic cells was augmented to a mild but significant extent by all-trans retinoic acid (ATRA) with concomitant upregulation of Connexin 43, a major component of gap junctions. Interestingly, HSV-TK/GCV killing was enhanced by expression of vesicular stomatitis virus G glycoprotein (VSV-G), a fusogenic membrane protein, which also increased leukemic cell fusion. Co-culture resistant cells expressing HSV-TK and cells stably transduced with VSV-G showed that expression of VSV-G could promote the bystander killing effect of HSV-TK/GCV. Furthermore, combination of HSV-TK/GCV with VSV-G plus ATRA produced more pronounced antileukemia effect. These results suggest that the HSV-TK/GCV system in combination with fusogenic membrane proteins and/or ATRA could provide a strategy to mitigate the chemoresistance of AML.

• Clinical and Experimental Pediatrics
• /
• 제52권6호
• /
• pp.713-716
• /
• 2009

안면 마비가 백혈병의 최초증상으로 발현되는 경우는 매우 드물고, 이들 대부분은 두개내 방사선 치료를 받는다. 이에 저자들을 백혈병의 최초증상으로 안면마비가 발현된 3례의 환자들을 보고하고자 한다. 3례 모두 두개내 방사선 치료없이 관해유도가 된 후 조혈모세포이식을 시행하였다. 2례는 동종이식 후 각각 52개월, 62개월까지 무사건 생존 중이고, 나머지 1례는 자가이식 후 재발의 최초증상으로 안면마비가 나타났고, 타인 조혈모세포이식 후 59개월째 무사건 생존 중이다. 2례에서 여전히 안면마비가 남아있긴 하지만, 두개내 방사선 치료 없이도 동종 조혈모세포이식으로 안면마비가 발현된 백혈병을 치료하여 이를 보고하고자 한다.