Impact of KIT D816 mutation on salvage therapy in relapsed acute myeloid leukemia with t(8;21) translocation / 中华血液学杂志

Objective: To evaluate the impact of KIT D816 mutation on the salvage therapy in relapsed acute myeloid leukemia (AML) with t(8;21) translocation. Method: The characteristics of the first relapsed AML with t(8;21) translocation from 10 hospitals were retrospectively collected, complete remission (CR(2)) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR(2) rate was analyzed. Results: 68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR(2). All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR(2) compared with non-KIT D816 group (23.1% vs 57.1%, χ(2)=7.559, P=0.006), and patients with longer CR(1) duration achieved significantly higher CR(2) than those with CR(1) duration less than 12 months (74.1% vs 31.9%, χ(2)=9.192, P=0.002). KIT D816 mutation was tightly related to shorter CR(1) duration. No significant difference of 2 years post relapse survival was observed between KIT D816 mutation and non-KIT D816 mutation group. Conclusion: KIT D816 mutation at diagnosis was an adverse factor on the salvage therapy in relapsed AML with t(8;21) translocation, significantly related to shorter CR1 duration, and can be used for prediction of salvage therapy response. KIT D816 mutation could guide the decision-making of salvage therapy in relapsed AML with t(8;21) translocation.

Effect of 1q21 amplification on bortezomib therapeutic response and prognosis of newly diagnosed multiple myeloma patients / 中华血液学杂志

Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions: 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.

Application of fresh amniotic membrane in microscopic adjustable suture surgery of intercommunity strabismus in childhood / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To discuss the clinical efficacy of fresh amniotic membrane ( AM ) during the microscopic adjustable suture surgery in children's intercommunity strabismus, in order to guide clinical treatment. METHODS: With the clinical randomized control study (RCT), 60 (112 eyes) cases of patients in childhood who received microscopic strabismus surgery in our hospital were divided them into two different groups from Jan. 2010 to Oct. 2015. According to the application of AM on the basis of ophthalmology outpatient number, 30 cases (58 eyes) in group A were treated with rectus muscle recession surgery combined adjustable suture combined with AM. The other 30 cases (54 eyes) in group B were treated with rectus muscle recession surgery combined adjustable suture only. All patients in two groups were followed-up over 6mo after the strabismus surgery. RESULTS:Twenty-seven cases ( 48 eyes ) of all the strabismus patients must be adjusted after strabismus surgery, and the eye position adjustment rate was 42.9%. At 1mo after surgery, eye position of 18 cases (29 eyes) can be adjusted in all patients, and 44. 8% (16 cases, 26 eyes ) in group A with the average of adjustment lengths was 2. 56±0. 64mm, and 5. 6% ( 2 cases, 3 eyes ) in group B, with the average of adjustment lengths was 0. 52±0. 28mm, the differences of the adjustment rate and the average of adjustment amount were both high statistically significant (χ2 =22.477, P CONCLUSION: The application of fresh AM in the microscopic adjustable suture strabismus surgery is exactly effective in treatment of children's intercommunity strabismus. It can significantly extend the adjustment time and increase the adjustment amount, and it also can statistically improve the controllability and achievement ratio for children's strabismus surgery.

Recent Advances of Research on CEBPA Mutation in Acute Myeloid Leukemia / 中国实验血液学杂志

CCAAT/enhancer binding protein alpha gene (CEBPA) is an important transcription factor in maintenance of differentiation of granulocyte series of hematopoietic system. It plays a key role in regulating cell proliferation and differentiation. CEBPA mutation easily occurs in M1 and M2 type of acute myeloid leukemia, about 5%-14% in adult acute myeloid leukemia and 7.9% in children with acute myeloid leukemia. At present, domestic CEBPA mutation research is far less than abroad. This review focuses on the structual characteristics and detection method of CEBPA, CEBPA clinical features, the effect of CEBPA mutation on the prognosis of patients and the choice of treatment.

Clinical characteristics and therapeutic efficacy of normal karyotype AML patients with CEBPA mutation / 中国实验血液学杂志

This study was aimed to explore the clinical characteristics and therapeutic efficacy of normal karyotype AML patients with CEBPA mutations. Fifty-five de novo AML patients with normal karyotype were retrospectively analyzed with regard to frequency of CEBPA mutation, clinical characteristics and therapeutic response. The results showed that CEBPA mutation was detected in 20 patients (36.4%), among them 17 cases displayed double mutations, three cases were with single mutation. The clinical characteristics of patients with CEBPA mutation displayed as follows: 75% of AML patients with CEBPA mutation were AML-M1 and AML-M2, the hemoglobin level at newly diagnosis was higher and the platelet count at newly diagnosis time was lower than those of AML patients without CEBPA mutation [(98.30 ± 20.33) g/L vs (81.69 ± 23.74) g/L (P < 0.05); and (33.30 ± 38.27) ×10(9)/L vs (64.79 ± 61.60) ×10(9)/L (P < 0.05)]. The leukemic cells highly expressed CD7 and CD34. The therapeutic efficacy of 1 cycle for AML patients with CEBPA mutation was satisfactory (72.2%), was higher than that of patients without CEBPA mutation(68.6%), but there was no statistical significance (P > 0.05). It is concluded that AML with CEBPA mutation is more observed in AML-M1 and AML-M2, and accompanies by high level of hemoglobin and lower platelet count, expression of CD7 and CD34. Early-term therapeutic efficacy is satisfactory. The frequency of CEBPA mutation may be higher in Chinese patients with AML compared with that reported in Western world.

Correlation of NPM1, FLT3-ITD mutations with leukocyte count and myeloblasts percentage in AML patients with normal karyotype / 中国实验血液学杂志

This study was aimed to investigate the correlation of NPM1 and FLT3-ITD mutations with leukocyte count in peripheral blood and bone marrow blasts in patients with acute myeloid leukemia (AML). Fifty-one acute myeloid leukemia patients with normal karyotype from January 2009 to December 2011 were enrolled in this study. The clinical data of 51 cases were analyzed retrospectively. Out of 52 cases 22 were male, and 29 were female. The median age was 47 years old (ranged from 14 to 83 years old). The de novo patients were examined by bone marrow cytomorphology and blood routine analysis. Polymerase chain reaction was used to analyze the NPM1 and FLT3-ITD mutations. The results showed that the patients with NPM1 mutations had higher leukocyte count compared with those without mutations (30.7×10(9)/L vs 8.6×10(9)/L, P = 0.002). FLT3-ITD mutation was related to higher leukocyte count (42.38×10(9)/L vs 11.45×10(9)/L without mutation, P = 0.033) and blasts (74.0% vs 60.25% without mutation, P = 0.036). The leukocyte count and percentage of bone marrow blasts were lowest in the patients with neither mutations, and gradually increasing in the NPM1(-) mutation, FLT3-ITD(-) mutation, and NPM1(+) mutation, FLT3-ITDI(+) mutation, and NPM1(+)/FLT3-ITD(+) mutation groups (P < 0.05). The patients tended to have NPM1 (P = 0.002) and FLT3-ITD (P = 0.033) mutations when their leukocyte counts were more than 12.55×10(9)/L and 37.85×10(9)/L, respectively. Those with bone marrow blast more than 72.25% showed higher rate of FLT3-ITD mutation (P = 0.008). Patients with NPM1 mutations had higher complete remission rate than those without NPM1 mutation (78.13% vs 40.0%, χ(2) = 4.651, P = 0.031) after remission induction therapy. It is concluded that both NPM1 and FLT3-ITD mutations are linked to higher leukocyte count and blast percentage, suggesting that both mutations may be associated with increased proliferation of leukemia cells, and may have a synergistic function in stimulating proliferation.

The study on relationship between age and cytogenetic subgroups in 640 patients with de novo acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the cytogenetic characteristics of different age subgroups in patients with acute myeloid leukemia (AML), and to explore the relationship between age and cytogenetics.</p><p><b>METHODS</b>Between January 2004 and December 2011, Bone marrow (BM) samples from 640 patients with de novo AML were analyzed retrospectively. The analyses were performed according to standard culturing and banding techniques, and clonal abnormalities were defined and described according to the International System for Human Cytogenetic Nomenclature (ISCN 2009). The cytogenetic subtypes were performed as normal, balanced, and unbalanced karyotypes. In the last group, the age distribution of complex and monosome karyotypes were further analyzed. The patients were divided into 8 age groups: 0 - 9, 10 - 19, 20 - 29, 30 - 39, 40 - 49, 50 - 59, 60 - 69, and ≥ 70 year old groups.</p><p><b>RESULTS</b>The distribution of normal, balanced, and unbalanced karyotypes showed age specific characteristics. The incidence of normal karyotype increased from 6.67% (0 ∼ 9 year old) to 58.33% (≥ 70) (χ(2) = 20.68, P = 0.001) and balanced karyotype decreased from 73.33% (0 ∼ 9) to 11.11% (≥ 70) (χ(2) = 48.22, P < 0.01). The frequency of unbalanced karyotypes increased from 20.0% (0 ∼ 9) to 30.56% (≥ 70) (χ(2) = 18.963, P = 0.008). The frequency of complex karyotype was 6.67% in 0 - 9 year old group, followed by 0% in 10 - 19 and 20 - 29 year old group, and from 1.72% to 11.11% from 30 - 39 to ≥ 70 year old group (χ(2) = 8.341, P = 0.08). Monosome karyotype was only detected in patients in 30 year old or older groups. Although an increased tendency was observed with ages, there was no significant difference (χ(2) = 4.778, P = 0.311).</p><p><b>CONCLUSION</b>The different age profiles of the cytogenetic subtypes may indicate the different mechanisms of the pathogenesis of AML, which may also offer beneficial information for etiological research of AML.</p>

Anti-leukemic effect of scutellaria extract SBX and its mechanisms / 中国实验血液学杂志

This study was aimed to explore the anti-leukemic effect of scutellaria extract SBX in human leukemia cell lines and its mechanism. The leukemia cell lines, including HL-60, NB4, U937, K562 and Jurkat, were cultured in vitro and proliferative inhibition of these cell lines was detected by CellTiter-Glo Luminescent Cell Viability Assay in order to screen the most sensitive cell line. The effect of SBX on cell cycle was analyzed by flow cytometry and the protein expressions determined by Protein Pathway Array respectively. The results indicated that SBX (10 - 200 µmol/L, for 72 h) significantly inhibited the proliferation of different leukemia cell lines in a dose-dependent manner (r value was 0.86, 0.88, 0.95, 0.94, 0.96, respectively), the HL-60 was the most sensitive cell line. Flow cytometric analysis showed that SBX (50, 10 µmol/L, for 48 h) arrested HL-60 cells in the G(0)/G(1) phase. In addition, protein expression of p-PKC α/βII, p-p38, Cdc25B, XIAP of HL-60 cells increased, and p-AKT, p-SAPK/JNK, Notch4, Cdk4, Cdc2, cyclin E, Akt, Bcl-2, Bax, cdc42, TNF-α, p27, CaMKKa decreased after exposure to SBX (50 µmol/L, for 48 h). It is concluded that SBX can inhibit the proliferation of different leukemia cell lines, and HL-60 is a sensitive cell line. SBX significantly influences EGFR, Ras/Raf/MAPK and Notch signaling pathway, through which effects the expression of cell cycle-related proteins resulting in arrest of HL-60 cells in G(0)/G(1).

Anti GVHD effect of the induction of immune tolerance in rats embryo / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate whether the fetal immune tolerance induction could replace the HLA typing for hematopoietic stem cell transplantation.</p><p><b>METHODS</b>Immune tolerance of SD rats was induced by injecting host Wistar rats peripheral blood mononuclear cells into yolk sac of the embryo, afterward the mature male offsprings were used as donor. The host female recipients received lethal dose irradiation and bone marrow transplantation(BMT). The Wistar rats transplanted with bone marrow from donor and unrelated SD rats as well as the rats which received radiation alone were used as control. The survival, histopathologically GVHD, the mental status, food and water intake, coat characteristics, activities were observed. Forty days after BMT, autologous and allogenous skin transplantation between donor and recipient rats was performed to observe the engraftment of solid organ.</p><p><b>RESULTS</b>The survival of the rats received bone marrow grafts from the immune tolerant donor was significantly longer than that of control groups (30 day survival rates were 86.7%, 6.7%, 0%, and 0% respectively), and there was no histopathologically GVHD observed, while in the sham group, the manifestations of GVHD was clearly visible. The skin engraftment rate between the host and the immune tolerant donor was significantly higher than that among non-related rats (84.6% and 0% respectively).</p><p><b>CONCLUSION</b>The induction of immune tolerance in embryo can overcome the HLA barrier and provide a good donor for hematopoietic stem cell and solid organ transplantation.</p>