[Comparison of the Prognostic Value of C-Reactive Protein to Albumin Ratio and Glasgow Prognostic Score in Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To compare the prognostic value of two predictive models based on C-reactive protein (CRP) and albumin (ALB), namely the CRP to ALB ratio (CAR) and the Glasgow prognostic score (GPS), in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The data of newly diagnosed DLBCL patients admitted to our center from May 2014 to January 2022 were reviewed. A total of 111 patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with detailed clinical, laboratory data and follow-up information were included. The receiver operating characteristic (ROC) curve was performed to evaluate the predictive value of pre-treatment CAR on disease progression and survival. Furthermore, the association between CAR and baseline clinical, laboratory characteristics of patients was evaluated, and progression-free survival (PFS) and overall survival (OS) were compared between different CAR and GPS subgroups. Finally, the univariate and multivariate COX propor-tional hazard regression models were used to analyze the factors affecting disease outcomes. RESULTS: ROC curve showed that the area under the curve (AUC) of CAR predicting PFS and OS in DLBCL patients was 0.687 (P =0.002) and 0.695 (P =0.005), respectively, with the optimal cut-off value of 0.11 for both predicting PFS and OS. Compared with the lower CAR (<0.11) group, the higher CAR (≥0.11) group had more clinical risk factors, including age >60 years (P =0.025), ECOG score ≥2 (P =0.004), Lugano stage III-IV (P < 0.001), non-germinal center B-cell-like (non-GCB) subtype (P =0.035), elevated lactate dehydrogenase (LDH) ( P < 0.001), extranodal involved site >1 (P =0.004) and IPI score >2 (P < 0.001). The interim response evaluation of patients showed that the overall response rate (ORR) and complete response rate (CRR) in the lower CAR group were both significantly better than those in the higher CAR group (ORR: 96.9% vs 80.0%, P =0.035; CRR: 63.6% vs 32.5%, P =0.008). With a median follow-up of 24 months, patients with lower CAR had significantly longer median PFS and OS than those with higher CAR (median PFS: not reached vs 67 months, P =0.0026; median OS: not reached vs 67 months, P =0.002), while there was no statistical difference in PFS (P =0.11) and OS (P =0.11) in patients with GPS of 0, 1, and 2. Multivariate Cox regression analysis indicated that only sex (male) and IPI score >2 were independent risk factors for both PFS and OS. CONCLUSION: CAR is significantly correlated with disease progression and survival in DLBCL patients; And compared with GPS, CAR has more advantages in predicting disease outcomes in DLBCL patients.

[Prognostic Value of Pre-treatment Albumin/Fibrinogen Ratio in Patients with Diffuse Large B-cell Lymphoma].

OBJECTIVE: To investigate the value of pre-treatment albumin/fibrinogen ratio (AFR) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The data of DLBCL patients in the Affiliated Hospital of North Sichuan Medical College from April 2014 to March 2021 were retrieved, and 111 newly diagnosed patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with complete data were included in the study. The clinical, laboratory examination and follow-up data of the patients were collected, and the receiver operating characteristic curve (ROC) was drawn according to patients' AFR before treatment and the survival status at the end of the follow-up, which could be used to preliminarily evaluate the predictive value of AFR for disease progression and patients' survival outcome. Furthermore, the correlation of AFR with the clinical and laboratory characteristics, progression-free survival (PFS) and overall survival (OS) was analyzed, and finally, univariate and multivariate Cox proportional hazard regression models were used to analyze factors affecting PFS and OS of DLBCL patients. RESULTS: The ROC curve indicated that AFR level had a moderate predictive value for PFS and OS in DLBCL patients, with the area under the curve (AUC) of 0.616 (P =0.039) and 0.666 (P =0.004), respectively, and the optimal cut-off values were both 9.06 for PFS and OS. Compared with high-AFR (≥9.06) group, the low-AFR (<9.06) group had a higher proportion of patients with Lugano III-IV stage ( P <0.001), elevated lactate dehydrogenase (P =0.007) and B symptoms (P =0.038). The interim analysis of response showed that the overall response rate (ORR) in the high-AFR group was 89.7%, which was significantly higher than 62.8% in the low-AFR group (P =0.001). With a median follow-up of 18.5 (3-77) months, the median PFS of the high-AFR group was not reached, which was significantly superior to 17 months of the low-AFR group (P =0.009). Similarly, the median OS of high-AFR group was not reached, either, which was significantly superior to 48 months of the low-AFR group (P < 0.001). In multivariate Cox regression analysis, AFR <9.06 was an independent risk factor both for PFS and OS (HR PFS=2.047, P =0.039; HR OS=4.854, P =0.001). CONCLUSION: Pre-treatment AFR has a significant value for the prognosis evaluation in newly diagnosed DLBCL patients.

Microstructural Evolution of SK85 Pearlitic Steel Deformed by Heavy Cold Rolling.

The microstructural evolution of SK85 pearlitic steel cold-rolled up to a 90% rolling reduction was characterized by scanning electron microscopy with electron backscattered diffraction (EBSD) and X-ray diffraction (XRD). SK85 steel exhibits excellent cold rolling performance. The interlamellar spacing of pearlite is refined obviously and a tensile strength of 2318 MPa can be reached for SK85 steel after 90% rolling reduction, an increase of 83% from 1264 MPa before rolling. The EBSD observation indicates that the {001} <110> texture becomes pronounced at a 90% rolling reduction in cold-rolled Sk85 steel. A propagation and multiplication of dislocations occur during rolling as the kernel average misorientation (KAM) angles significantly increase from 0.72° to 2.11°. The XRD analysis reveals that bcc ferrite is transformed into a bct structure at a 90% rolling reduction. The strengthening mechanism was discussed.

Effect of CO2 on the Desulfurization of Sintering Flue Gas with Hydrated Lime.

The effect of carbon dioxide (CO2) on the desulfurization of sintering flue gas with hydrate (Ca(OH)2) as an absorbent was investigated, and the formation of calcium carbonate (CaCO3) and its effect on the desulfurization was discussed. The competitive relationship between carbon dioxide (CO2) and sulfur dioxide (SO2) with the deacidification agent in sintering flue gas is discussed thermodynamically, showing that sulfates are more likely to be generated under high oxygen potential conditions and that SO2 reacts more preferentially than CO2 under a thermodynamic standard state. The amount of produced CaCO3 increases under the condition that the CO2 concentration is absolutely dominant to SO2 in the sintering flue gas atmosphere. The effect of temperature, humidity and CO2 concentration on the desulfurization of Ca(OH)2 are discussed experimentally. The increasing temperature is not conducive to desulfurization, and the humidity can promote desulfurization, while excessive humidity could inhibit desulfurization. The suitable relative humidity is 20%. In situ generated calcium carbonate has a certain desulfurization effect, but the desulfurization effect is not as good as Ca(OH)2. However, a large proportion of CaCO3 was produced in the desulfurization ash under the condition that CO2 concentration was absolutely dominant to SO2 in the sintering flue gas atmosphere.

Daratumumab for Refractory IgD Multiple Myeloma with Lung Cancer and Persistent Thrombocytopenia: a Case Report.

BACKGROUND: Immunoglobulin D multiple myeloma (IgD-MM) is a rare but aggressive disease. The safety and effectiveness of anti-CD38 monoclonal antibody (daratumumab) have not been known in either IgD-MM or MM complicated with secondary neoplasm. METHODS: A fragile IgD-MM patient had an aggressively relapsed disease concurrent with lung cancer and severe thrombocytopenia, which led to a dilemma for management. After a failure of ixazomib-based chemotherapy, a salvage therapy with daratumumab unexpectedly induced complete remission and platelet recovery, and the patient successfully proceeded to lung cancer surgery. CONCLUSIONS: Our case indicates daratumumab is both safe and effective for refractory IgD-MM with severe complications.

[Predictive Value of Pre-treatment Serum Uric Acid Level for Prognosis in Newly Diagnosed Patients with Multiple Myeloma].

OBJECTIVE: To evaluate the predictive value of pre-treatment serum uric acid (sUA) level for the prognosis of newly diagnosed multiple myeloma (NDMM) patients. METHODS: The NDMM patients admitted to our center from January 2014 to December 2018 were analyzed retrospectively, and 94 patients among them who were initially treated with bortezomib-based chemotherapy for at least 4 cycles were included in this study. Clinical characteristics, laboratory data and follow-up information were collected, and the predictive value of sUA on the overall survival (OS) of NDMM was evaluated by using receiver operating characteristic (ROC) curve based on the patient's pre-treatment sUA level and the survival status at the end of follow-up, and the correlation of the sUA level with patient's clinical, laboratory characteristics and overall survival (OS) was further analyzed. The univariate and multivariate Cox proportional-hazards model were used to identify the potential factors affecting OS. RESULTS: ROC analysis showed that the area under the curve for predicting OS in NDMM patients with sUA level was 0.702 (P<0.001), and the optimal cut-off value was 455.4 µmol/L. Compared to patients with low sUA (<455.4 µmol/L), patients with higher sUA (≥455.4 µmol/L) were more likely to have international staging system (ISS) stage III disease, beta2-microglobulin (ß2-MG) ≥5.5 mg/L, serum creatinine (sCr) ≥177 µmol/L, serum corrected calcium (cCa) ≥2.75 mmol/L, urea nitrogen (BUN) ≥1×upper limit of normal, and high-risk cytogenetic abnormality (all with P<0.001). At a median follow-up of 22.5 months, the OS of NDMM with lower sUA was significantly better than higher sUA (median OS: not reached vs 32 months, P=0.003). Univariate COX regression analysis identified that age ≥60 years old, ISS stage III, sUA ≥455.4 µmol/L, ß2-MG ≥5.5 mg/L, cCa ≥2.75 mmol/L were risk factors affecting OS. The multivariate COX regression analysis that only age ≥60 years old (HR=2.317, 95%CI: 1.015-5.288, P=0.045) and sUA ≥455.4 µmol/L (HR=2.785, 95%CI: 1.054-7.361, P=0.039) were independent risk factors affecting OS. CONCLUSION: Pre-treatment sUA level is a potential biomarker for the prognosis evaluation in NDMM patients, which deserves a further exploration and verification.

[Short-Term Efficacy and Safety Profile of Generic Bortezomib in the Treatment of Multiple Myeloma].

OBJECTIVE: To investigate the short-term efficacy and safety of generic bortezomib in the treatment of Chinese patients with multiple myeloma (MM). METHODS: Clinical data of 62 MM patients (median age of 62 years) who had accepted at least 2 cycles of chemotherapy based on generic bortezomib in our center from December 2017 to July 2019 were retrospectively analyzed, including 47 newly diagnosed patients and 15 with disease recurrence or progression. RESULTS: Anemia, renal dysfunction, hypoproteinemia and high level of ß 2-microglobulin were all improved rapidly after induction treatment. In 56 patients who had completed at least 4 cycles of chemotherapy, the overall response rate (ORR) was 85.7%, and 64.3% of the patients achieved very good partial response (VGPR) or better, and 28.6% achieved complete remission (CR) or better. In the 19 patients who had already completed all planned induction and consolidation treatment (9 cycles of chemotherapy or 4-6 cycles of chemotherapy plus autologous hematopoietic stem cell transplantation), 84.2% achieved VGPR or better, and 57.9% achieved CR or stringent complete remission (sCR). Median follow-up time was 300 days with data cut-off date of September 20, 2019, and the progression-free survival (PFS) rate and overall survival (OS) rate were 62.1% and 85.3%, respectively. The possible adverse reactions associated with bortezomib were grade 1-2, the most common hematologic adverse reaction was thrombocytopenia (27.4%), and the most common non-hematologic adverse reaction was peripheral neuropathy (43.5%), followed by asthenia (37.1%). CONCLUSION: The disease severity can be rapidly alleviated after generic bortezomib-based chemotherapy, and a favorable short-term efficacy and survival have been observed with a generally acceptable toxicity profile. However, the long-term outcomes will be examined through further follow-up.

Electronic Structure and Oxidation Mechanism of Nickel-Copper Converter Matte from First-Principles Calculations.

The structural and electronic properties of Cu1.96S and Ni3S2 present in nickel-copper converter matte and sulfides such as CuS, Ni7S6, NiS, Ni3S4, and NiS2, likely existing as intermediates in the oxidative leaching of the matte, were investigated using first-principles calculations. Analyses of the total and partial density of states (DOS), with electron density and differential charge density, show that Cu-S and Ni-S bonds are of covalent character, and as the ratio of Ni/Cu to S decreases for the sulfides, Cu/Ni-3d orbital energies shift downward, while S-3p orbital energies shift upward. According to the values of their Cu/Ni-3d band centers, the oxidation activity decreases in the order Cu1.96S > Ni3S2 > Ni7S6 > NiS > Ni3S4 > NiS2 > CuS. This oxidation sequence leads to thermodynamically favorable substitution reactions between the nickel sulfides and Cu2+ for obtaining more stable CuS, which is the theoretical basis of Sherritt Gordon's selective leaching process.

[Effect of High Dose Vitamin C on Proliferation and Apoptosis of Acute Myeloid Leukemia Cells].

OBJECTIVE: To investigate the effects of high dose vitamin C on proliferation and apoptosis of acute myeloid leukemia (AML) cell lines including HL-60, U937 and primary CD34+ leukemia cells in AML. METHODS: CD34+ cells were sorted by using immunomagnetic cell sorting system, then the primary CD34+ leukemia cells, including HL-60 and U937 cell lines were cultured in vitro. Cells in each group were treated with different concentrations of vitamin C, the survival rate of cells was determined by MTT assay, the apoptosis rate of cells was evaluated by Annexin V/PI double staining, the expression of apoptotic proteins-including cleaved caspase 3, cleaved caspase-9 and cleaved PARP were detected by Western blot. RESULTS: The proliferation of HL-60 and U937 cells could be inhibited by high dose vitamin C, which showed a concentration-dependent manner (r=-0.9664; r=-0.9796). HL-60 and U937 cells were treated with different concentrations of vitamin C (8 and 20 mmol/L) for 24 hours, respectively, it was found that with the increasing of vitamin C concentration, cell apoptosis rate was significantly increased (r=0.9905; r=0.9971), and the expression of apoptosis related proteins including cleaved caspase 3, cleaved caspase-9 and cleaved PARP was aslo significantly increased with the increasing of concentration. In addition, it was found that with or without the mutation of TET2, high dose vitamin C could inhibit the proliferation (r=-0.9719; r=-0.9699) and promote the apoptosis (r=0.9998; r=0.9901) of primary CD34+ leukemia cells in AML, which showed a dose-dependent manner, but it showed no effect on the proliferation (r=-0.2032) and apoptosis (r=0.1912) of normal CD34+ cells. CONCLUSION: High dose vitamin C can inhibit the proliferation and promote the apoptosis of acute myeloid leukemia cells, and selectively kill primary CD34+ leukemia cells in AML.

Long non-coding RNA taurine-upregulated gene 1 correlates with unfavorable prognosis in patients with refractory or relapsed acute myeloid leukemia treated by purine analogue based chemotherapy regimens.

OBJECTIVE: This study aimed to explore the correlation of long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) expression with clinicopathological features and its predictive value for treatment response and survival profiles in refractory or relapsed acute myeloid leukemia (R/R AML) patients. METHODS: Seventy three R/R AML patients who received cladribine combined with cytarabine and granulocyte colony-stimulating factor (G-CSF) (CLAG) or fludarabine combined with cytarabine and G-CSF (FLAG) based chemotherapy and 37 non-malignant controls were recruited. LncRNA TUG1 expression was detected in bone marrow sample obtained before treatment. Complete response (CR), partial response (PR), overall response rate (ORR) and overall survival (OS) were evaluated. RESULTS: LncRNA TUG1 expression was upregulated in R/R AML patients compared to controls. It was also elevated in R/R AML patients with age ⩾ 60 years (vs. age < 60 years, P= 0.030) and in patients with secondary AML (vs. primary AML, P= 0.035). R/R AML patients with lncRNA TUG1 high expression achieved numerically lower CR (P= 0.053), decreased ORR (P= 0.028) and shorter OS (P< 0.001) than patients with lncRNA TUG1 low expression. Univariate logistic regression and COX's regression disclosed that lncRNA TUG1 high expression correlated with declined ORR, numerically decreased CR, and reduced OS. Furthermore, multivariate analyses verified that lncRNA TUG1 high expression was an independent predictive factor for decreased ORR and worse OS. CONCLUSIONS: In conclusion, lncRNA TUG1 expression was elevated in R/R AML patients, and it might serve as a potential biomarker for poor prognosis in R/R AML patients treated with CLAG or FLAG based chemotherapy.

Targeting of heme oxygenase-1 attenuates the negative impact of Ikaros isoform 6 in adult BCR-ABL1-positive B-ALL.

The correlation between Heme oxygenase-1 (HO-1) and dominant-negative Ikaros isoform 6 (IK6) is unclear. Firstly, we detected that IK6 existed in 20 of 42 (47.6%) adult BCR-ABL1-positive B-lineage acute lymphoblastic leukemia (BCR-ABL1-positive B-ALL) by using reverse transcribed polymerase chain reaction (PCR) and nucleotide sequencing. IK6-positive patients had an unfavorable outcome compared with IK6-negative ones. Further study showed that the level of HO-1 expression was higher in IK6-positive patients' samples than that in IK6-negative ones. And there was a strong correlation between the expression of IK6 and HO-1. The growth of primary CD34+ leukemic cells derived from our IK6-positive patients' pool was prohibited by silencing HO-1, further promoting their apoptosis. Furthermore, primary CD34+ leukemic cells derived from IK6-positive patients shown poor responses to imatinib in comparison with wild-type (IK1) patients, suggesting that the expression of IK6 resisted to imatinib in adult BCR-ABL1-positive B-ALL. Importantly, inhibition of HO-1 also increased their sensitivity to tyrosine kinase inhibitors (TKIs). Finally, we found that IK6 activated downstream STAT5, and HO-1 was one of the downstream target genes of STAT5. In conclusion, HO-1 is an essential survival factor in BCR-ABL1-positive B-ALL with IK6, and targeting HO-1 can attenuate the negative impact of IK6.

Donor-Derived Regulatory T Cells Attenuate the Severity of Acute Graft-Versus-Host Disease after Cord Blood Transplantation.

Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is a curative therapy for some types of hematological disorders. However, allo-PBSCT is commonly complicated with acute graft-versus-host disease (aGVHD), characterized by host tissues being attacked by the grafted donor lymphocytes due to disparities of human leukocyte antigen (HLA) between the donor and host. By contrast, cord blood transplantation (CBT) is typically associated with low-grade severity of aGVHD, but the underlying mechanisms remain unclear. Donor-derived CD4(+) alloreactive T cells (ATs) are of a specific lymphocyte subset, which can be activated by the recipient's HLA, and play a crucial role in the onset of aGVHD. In the present study, we aimed to explore the difference in the property of CD4(+) ATs between cord blood (CB) and adult peripheral blood (APB). We thus found that CB and APB CD4(+) ATs contained not only effector T cells (Teffs) that execute aGVHD, but also a distinct subset of FoxP3(+) regulatory T cells (Tregs) that may alleviate aGVHD. Importantly, CB CD4(+) ATs contained higher percentage of FoxP3(+) Tregs, compared to APB CD4(+) ATs (P < 0.001), while lower percentage of Teffs (Th1, Th2 and Th17 cells) was detected in CB CD4(+) ATs (P < 0.05, P < 0.001 and P < 0.05, respectively). Our findings suggest that FoxP3(+) Tregs in CB CD4(+) ATs may contribute to attenuating the severity of aGVHD observed after CBT.

Potential role of exosome-associated microRNA panels and in vivo environment to predict drug resistance for patients with multiple myeloma.

Multiple myeloma (MM) is the second most common hematologic neoplasms and an appropriate in vivo environment for myeloma cells has potential implications for initiation, progression, and metastasis of MM. Exosomes, entities carrying microRNAs (miRNAs) to target locations, participate in the cross-talk between myeloma cells and nonmalignant components of the in vivo environment. This study disclosed the emerging roles of circulating exosome-associated miRNAs in drug resistance (DR) of MM. To this end, the medical records of consecutively hospitalized MM patients, who received novel agents-based therapies, were analyzed. Then, an optimized procedure was established for exosome isolation and exosomal RNA analysis. The exosome-associated miRNA expression patterns for predicting bortezomib (Bz) resistance of MM were further examined using a microarray. In total, 204 patients were enrolled with DR rates of 36.5%, 73.1% and 81.8% in the bortezomib (Bz), thalidomide and lenalidomide containing groups. The serum total light chain ratio ≥ 100, CRP ≥ 20 mg/L, and the second-line usage increased risks of acquired Bz-resistance. Among 68 cases having genetic tests, a high risk factor for predicting de novo DR was 1q21 amplification, which also correlated with lower levels of cholesterol and LDL-C. Moreover, nano-sized exosomes were isolated with significantly increasing internal RNAs and down-regulation of exosomal miR-16-5p, miR-15a-5p and miR-20a-5p, miR-17-5p was revealed in the patients resistant to Bz. The routine workup of MM hardly suggested a value for DR prediction. The circulating exosomes carrying miRNAs provided a window that permits a better understanding of the in vivo intercellular crosstalk in MM patients.

[FLT3 mutation in acute promyelocytic leukemia patients with extramedullary relapse].

OBJECTIVE: To evaluate the role of FLT3 gene mutation in acute promyelocytic leukemia (APL) patients with extramedullary relapse. METHODS: The blood and bone marrow samples were collected from 2 APL patients with extramedullary relapse and FLT3 gene mutation was detected with these samples. The correlation between FLT3 gene mutation and extramedullary relapse was analyzed. RESULTS: A rare point mutation Asn841Gly (A841G) of FLT3-TKD and a novel mutation (c. 1209_1210insT/p. K404X) of WT1 were detected in a APL patient who suffered CNS relapse, while a rare point mutation Asp839Gly (D839G) of FLT3-TKD and a novel mutation Arg458Pro (c. 1373G>C) of WT1 were found in another APL patient who suffered testicular relapse. CONCLUSION: The rare point mutation of FLT3 as well as the novel mutation of WT1 were found in APL with extramedullary relapse.

Acute promyelocytic leukemia with Flt3-TKD and WT1 mutations relapsing in a testicle and followed by systemic relapse.

Extramedullary relapse is a rare phenomenon in patients with acute promyelocytic leukemia (APL), especially that derived from urogenital systems like the testicles. In this report, we describe an APL patient who had received standard induction/maintenance therapy resulting in durable remission for 4.5 years, when he presented with a unilateral testicular mass confirmed as myeloid sarcoma; this was followed by systemic relapse of APL. Retrospective analysis of the involved blood and bone marrow samples at the time of the initial diagnosis revealed a rare point mutation of FLT3-TKD and a novel mutation of WT1. These mutations were detected recurrently throughout the course of the disease. After reinduction therapy with arsenic trioxide and all-trans retinoic acid combined with daunorubicin, complete hematological remission was achieved for the ensuing salvage allogeneic hematopoietic stem cell transplant.

Long-term culture of leukemic bone marrow primary cells in biomimetic osteoblast niche.

We constructed a "biomimetic osteoblast niche" with bio-derived bone as a scaffold, on which we seeded marrow mesenchymal stem cells (MSCs) from CML patients, and induced the MSCs to differentiate into osteoblasts. Bone marrow mononuclear cells from CML patients were cultured in the biomimetic niche (3D culture system) or a 2D culture system with the induced MSCs/osteoblasts as a feeder cell layer for 2 and 5 weeks without adding exogenous cytokines. Cultured cells were analyzed regarding their phenotypes and functions using flow cytometry, colony-forming unit (CFU) assay and long-term culture-initiating cells (LTC-IC) assay. All cultured and colony cells in the LTC-IC assay were collected and analyzed by fluorescent in situ hybridization to identify Ph (bcr/abl)-positive cells. Our results showed that all parameters were higher in the 3D than in the 2D system, either at 2 or 5 weeks, i.e., regarding the number of CD34(+) cells (8,277.00 vs. 4,490.75 or 2,276.75 vs. 786.00 per well on average, respectively), number of CD34(+)/CD38(-) cells (1,207.50 vs. 474.25 or 497.25 vs. 114.25 per well on average, respectively), numbers of CFUs (103.33 vs. 79 or 47.0 vs. 21.67/10(5) MNCs; 189.33 vs. 131.00 or 10.33 vs. 3.67 per well on average, respectively), frequency of LTC-ICs (2.23 x 10(-5) vs. 1.40 x 10(-5) or 1.86 x 10(-5) vs. 0.64 x 10(-5), respectively) and number of remaining LTC-ICs (2.80 vs. 2.03 or 0.46 vs. 0.07 per well on average, respectively). The Ph (bcr/abl)-positive cell fraction was reduced in both systems during culture, but in the 3D system, it was not as rapid as in the 2D system and showed a leukemic predominance. In conclusion, our "biomimetic osteoblast niche" might provide a more adaptive microenvironment for leukemic stem/progenitor cell growth. The biological characteristics of leukemic stem/progenitor cells were partially maintained. It was suggested that the 3D biomimetic niche might be a new tool for studying the behaviors of leukemic hematopoietic stem cells/hematopoietic progenitor cells in vitro.

[Expression of tumor suppressor gene pten in patients with myelodysplastic syndrome and acute myeloid leukemia].

To study the expression and significance of pten gene in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), RT-PCR and Western blot were respectively applied to detect pten mRNA and PTEN protein in Jurkat cells (as negative control), in bone marrow nucleated cells of 35 patients with MDS, 45 patients with AML and 20 normal control. The results showed that pten mRNA expression could not be detected in Jurkat cells, and the positive rate in MDS patients (77.1%) was significantly lower than that in normal control group (90.0%) (p > 0.05), while significant difference was found between AML patients and normal control (60.0% vs 90.0%, p < 0.05); the positive rate in MDS-RAEB patients (70.0%) was lower than that in MDS-RCMD (86.7%); positive rate in de novo and relapsed AML patients (53.3%) was lower than that in AML patients in CR (73.3%), but statistics tests did not show significant difference (p > 0.05). The results of relative expression level of pten mRNA in all groups indicated that both relative expression levels in MDS patients and AML patients were definitely lower than that in normal control group (p < 0.005); the relative expression level in MDS-RAEB patients was lower than that in MDS-RCMD patients (p < 0.05); and in de novo and relapsed AML patients was obviously lower than that in AML patients in CR (p < 0.001). However, there was no significant difference between MDS and AML patients (p > 0.05). The positive rate of PTEN protein expression in both MDS (65.7%) and AML (54.8%) patients were lower than that in normal control (90.0%) (p < 0.05), and there was no significant difference when comparing MDS-RCMD patients (80.0%) with MDS-RAEB patients (55.0%) (p > 0.05), but positive rate of PTEN protein expression in de novo and relapsed AML patients (44.4%) was significantly lower than that in AML patients in CR (73.3%) (p < 0.05). It is concluded that the complete loss of pten mRNA in MDS and AML is uncommon, but the relative expression level in both diseases is significantly lower than that in normal people. The positive rates of PTEN protein expression in both MDS and AML patients are lower, compared with normal people, but are not in accordance with the expression of pten mRNA. The abnormalities of pten gene expression may be involved in the pathogenesis of MDS and AML.