Naturally selected CD7 CAR-T therapy without genetic editing demonstrates significant antitumour efficacy against relapsed and refractory acute myeloid leukaemia (R/R-AML).

BACKGROUND: The survival rate for patients with relapsed and refractory acute myeloid leukaemia (R/R-AML) remains poor, and treatment is challenging. Chimeric antigen receptor T cells (CAR-T cells) have been widely used for haematologic malignancies. Current CAR-T therapies for acute myeloid leukaemia mostly target myeloid-lineage antigens, such as CD123 and CD33, which may be associated with potential haematopoietic toxicity. As a lineage-specific receptor, CD7 is expressed in acute myeloid leukaemia cells and T cells but is not expressed in myeloid cells. Therefore, the use of CD7 CAR-T cells for R/R-AML needs to be further explored. METHODS: In this report, immunohistochemistry and flow cytometry were used to analyse CD7 expression in clinical samples from R/R-AML patients and healthy donors (HDs). We designed naturally selected CD7 CAR-T cells to analyse various functions and in vitro antileukaemic efficacy based on flow cytometry, and xenograft models were used to validate in vivo tumour dynamics. RESULTS: We calculated the percentage of cells with CD7 expression in R/R-AML patients with minimal residual disease (MRD) (5/16, 31.25%) from our institution and assessed CD7 expression in myeloid and lymphoid lineage cells of R/R-AML patients, concluding that CD7 is expressed in T cells but not in myeloid cells. Subsequently, we designed and constructed naturally selected CD7 CAR-T cells (CD7 CAR). We did not perform CD7 antigen knockdown on CD7 CAR-T cells because CD7 molecule expression is naturally eliminated at Day 12 post transduction. We then evaluated the ability to target and kill CD7+ acute myeloid leukaemia cells in vitro and in vivo. Naturally selected CD7 CAR-T cells efficiently killed CD7+ acute myeloid leukaemia cells and CD7+ primary blasts of R/R-AML patients in vitro and significantly inhibited leukaemia cell growth in a xenograft mouse model. CONCLUSION: Naturally selected CD7 CAR-T cells represent an effective treatment strategy for relapsed and refractory acute myeloid leukaemia patients in preclinical studies.

CAR-T bridging to allo-HSCT as a treatment strategy for relapsed adult acute B-lymphoblastic leukemia: a case report.

BACKGROUND: Adults with relapsed acute lymphoblastic leukemia (ALL) have a poor prognosis, especially in patients who relapsed within 6 months of complete remission 1 (CR1). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the treatment of choice. However, this can only be considered after complete remission 2 (CR2) is achieved. Therefore, bridging treatment is urgently needed. CASE PRESENTATION: In the present study, we report a relapsed adult B-cell ALL case that achieved CR2 after treatment with CD19-directed chimeric antigen receptor (CAR)-modified T cell (CAR-T) therapy. After subsequent allo-HSCT, the patient acquired 21 months of disease-free survival. CONCLUSION: The present results confirm that both CAR-T and allo-HSCT are effective for treating refractory or relapsed B-ALL. However, a novel sequential treatment strategy with these two therapeutic methods may achieve longer disease-free survival time.

The novel HLA-C*07:1029 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*07:1029 differs from HLA-C*07:02:01:01 by one nucleotide in exon 5.

Impact of Early Natural Killer Cell Reconstitution on the Outcomes of T Cell-Replete Allogeneic Hematopoietic Stem Cell Transplantation.

Background: Early immune reconstitution is crucial to successful outcomes after allogeneic stem cell transplantation (allo-HSCT). However, in T cell-replete HSCT, the impact of natural killer (NK) cells on transplantation outcome and the factors influencing early NK cell reconstitution remain unclear. Methods: In this retrospective study, we analyzed 128 patients with hematological malignancies who received the first T cell-replete allo-HSCT between May 2019 and September 2021. After application of a conditioning regimen, prophylaxis for graft versus host disease (GVHD), and engraftment, the patients received prevention and treatment procedures for cytomegalovirus (CMV) reactivation. NK cells, T lymphocytes and B lymphocytes in peripheral blood were collected and analyzed at 30, 60, 90, 135 and 180 days after transplantation to observe immune cell reconstitution. Overall survival (OS), relapse-free survival (RFS), minimal residual disease (MRD), relapse, and non-relapse mortality (NRM) were evaluated. SPSS 25.0 and R version 4.2.1 were used for statistical analysis. Results: In patients with rapid NK recovery (NK cell count at 30 days post-HSCT [NK30] >165/µL and 60 days post-HSCT [NK60] >265/µL), we observed lower rates of NRM, CMV reactivation and acute GVHD (aGVHD). Multivariate analysis indicated that a lower NK30 (≤165/µL) was an independent factor associated with inferior OS and RFS. The NK30 and NK60 in patients with CMV reactivation and aGVHD after transplantation were significantly lower than those in patients without these complications. In addition, CD107a expression in NK cells was also significantly lower in patients who experienced aGVHD. Correlation analysis did not find an inhibitory effect of T-lymphocyte subset reconstitution on NK cells in the early stage after transplantation. Conclusion: Rapid NK cell reconstitution early after allo-HSCT had protective effects on NRM and survival. Promoting early NK cell reconstitution represents a new approach to improving the outcomes of allo-HSCT.

The different variant allele frequencies of type I/type II mutations and the distinct molecular landscapes in CALR-mutant essential thrombocythaemia and primary myelofibrosis.

OBJECTIVE: Calreticulin (CALR) mutations have been identified as driver mutations in a quarter of patients with essential thrombocythaemia (ET) and primary myelofibrosis (PMF), which are subgroups of myeloproliferative neoplasms (MPNs). A 52-bp deletion (type I mutation) and a 5-bp insertion (type II mutation) are the most frequent variants. To better understand the impact of different CALR mutant variants, with or without nondriver mutations, on the clinical subtypes of MPN needs further investigation. METHODS: The clinical characteristics, laboratory parameters and genetic mutation statuses were analysed in a cohort of 77 MPN patients with CALR mutations (ET = 24, prePMF = 33, and overt PMF = 20). Targeted NGS using a 38-gene panel was performed to evaluate the variant allele frequency (VAF) of CALR type I/type II mutations and assess the molecular landscape of nondriver gene mutations. RESULTS: A lower VAF of type I vs. type II was observed in CALR-mutant ET, prePMF and overt PMF, and a higher frequency of type I vs. type II was found in CALR-mutant overt PMF. Additional somatic mutations were indicated to be useful in understanding the pathogenesis of MPN. In this study, the mutation landscape was more complex in overt PMF than in ET or in prePMF. Mutations in epigenetic regulators (ASXL1, EZH2 and TET2) were more common in overt PMF. CONCLUSIONS: The two different subtypes of CALR mutations may have different impacts on MPN. A lower VAF of CALR type I indicates a greater contribution to disease progression in MPN, and increased nondriver mutations may be important in myelofibrosis progression.

[Analysis of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Hematological Malignancies: A Single-center Study].

OBJECTIVE: To analyze the survival, prognostic factors, and prevention of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological malignancies, and explore the relationship between immune reconstruction, loss of human leukocyte antigen (HLA-loss) and relapse after transplantation. METHODS: From July 2012 to June 2020, 47 patients with hematological malignancies who relapsed after allo-HSCT were retrospectively analyzed, including 20 cases undergoing matched-sibling donor transplantation (MSD), 26 cases undergoing haploidentical transplantation (HID), and 1 case undergoing matched-unrelated donor transplantation (MUD). Multivariate analysis was used to analyze the risk factors related to post-relapse overall survival (PROS). RESULTS: All the 47 patients were implanted successfully. The cumulative incidence of grade Ⅱ-Ⅳ, Ⅲ/Ⅳ acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) was 40.4%, 10.6%, and 31.9%, respectively. The incidence of grade Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD in HID group was 42.3% and 11.5%, while in MD group was 38.1% and 9.5% (P=0.579, P=1.000), and the incidence of cGVHD in the two groups was 34.6% and 28.6% (P=0.659). The PROS of patients with NK cell absolute count > 190 cells/µl 30 days after transplantation was higher than that of patients with NK cell absolute count ≤190 cells/µl (P=0.021). The 1-year and 3-year PROS of all the patients was 68.1% and 28.4%, respectively, while in the HID group was 78.9% and 40.3%, in the MD group was 54.4% and 14% (P=0.048). Multivariate analysis showed that grade Ⅱ-Ⅳ aGVHD and time of relapse < 3 months were independent risk factors of PROS (P<0.05). CONCLUSION: The therapeutic effect of haploidentical transplantation in patients with relapsed hematological malignancies after allo-HSCT is better than that of matched donor transplantation. The high absolute count of NK cells 30 days after transplantation can increase PROS. Grade Ⅱ-Ⅳ aGVHD and time of relapse < 3 months have prognostic significance for long-term survival of patients with relapsed hematological malignancies after transplantation.

A visual model for prognostic estimation in patients with primary diffuse large B-cell lymphoma of small intestine and colon: analysis of 1,613 cases from the SEER database.

BACKGROUND: Treatment modalities for primary diffuse large B-cell lymphoma of Small intestine and colon (PIC-DLBCL) have changed significantly during the past decades. However, limited information on the trends of clinical outcome of PIC-DLBCL patients has been reported, and the influence of marital status and medical insurance on prognosis is ignored. METHODS: This was a retrospective analysis the survival of PIC-DLBCL patients using the Surveillance, Epidemiology, and End Results (SEER) database between 2002 and 2016. The patients were divided into the training and validation cohort. In the training cohort, univariate and multivariable Cox regression analysis, Log-rank test and the Kaplan-Meier method were used to find out the independent prognostic factors, from which the visual prognostic model (nomogram and graphical web page) was established. C-index and calibration plots were used to evaluate the prediction accuracy of the model. In the validation cohort, both Decision curve analysis (DCA) and Receiver operating characteristic (ROC) curve was performed to compare the model with the International Prognostic Index (IPI) scoring model which is universally used to estimate prognosis of PIC-DLBCL. RESULTS: A total of 1,613 patients were collected, and the 5-year overall survival of all cases was 64.5%. Age at diagnosis (HR =2.58, 95% CI: 2.29-2.91), Ann Arbo stage (HR =1.34, 95% CI: 1.24-1.44), Divorced or Separated (HR=1.21, 95% CI: 1.06-1.38), Uninsured (HR =1.32, 95% CI: 1.19-1.45) and Primary colon (HR =1.23, 95% CI: 1.08-1.40) were associated with prognosis and were used to build up the visual model (nomogram and graphical web page). Both DCA and ROC curve showed that the model had better authentication capability than the IPI scoring model (AUC 0.820 vs. 0.714). The calibration plots showed that the model could accurately predict patient prognosis. CONCLUSIONS: The visual model could output individual estimate prognosis simply and correctly, including marital status and medical insurance for the first time. Consideration of both medical and social factors, this study provided a new way to explore the improving prognosis of PIC-DLBCL.

Programmed cell death protein-1 inhibitor combined with chimeric antigen receptor T cells in the treatment of relapsed refractory non-Hodgkin lymphoma: A case report.

BACKGROUND: Chimeric antigen receptor T cell (CART) therapy has benefited many refractory lymphoma patients, but some patients experience poor effects. Previous studies have shown that programmed cell death protein-1 (PD-1) inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment. CASE SUMMARY: A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema. A large mass was detected in the pelvis, and pathology indicated non-Hodgkin diffuse large B-cell lymphoma. After three cycles of the R-CHOP chemotherapeutic regimen, the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine. Pathological examination of the nodules indicated DLBCL again. The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma. We recommended CAR-T cell treatment. Before treatment, the patient's T cell function and expression of immune detection points were tested. Expression of PD-1 was obviously increased (52.7%) on cluster of differentiation (CD)3+ T cells. The PD-1 inhibitor (3 mg/kg) was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide. CAR-CD19 T cells of 3 × 106/kg and CAR-CD22 T cells 1 × 106/kg were infused, respectively. The therapeutic effect was significant, and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable. Presently, the patient has been disease-free for more than 12 mo. CONCLUSION: This case suggests that the combination of PD-1 inhibitors and CAR-T cells improved therapeutic efficacy in B-cell lymphoma.

Rituximab for acute demyelinating myelopathy after allogeneic hematopoietic stem cell transplantation: a case report.

Acute demyelinating myelopathy after allogeneic hematopoietic stem cell transplantation (HSCT) is rare, and the exact pathogenesis remains unclear. Here, we report the case of a 20-year-old patient with B-cell acute lymphocyte leukemia (B-ALL) who developed acute demyelinating myelopathy approximately 10 months after HSCT. Magnetic resonance imaging revealed high T2 signal intensity lesions from the C2-T4 levels of the spinal cord. Treatments with high doses of corticosteroids, immunoglobulins, and rituximab improved his neurologic symptoms, and he achieved 44 months of leukemia-free and graft-versus-host disease (GVHD)-free survival, with no recurrence of the demyelination myelopathy. An understanding of the contribution of immune reconstitution to the pathogenesis of demyelinating myelopathy after HSCT and the association of this disease with GVHD will require more clinical cases.

[As2O3 induces demethylation and up-regulates transcription of SHP-1 gene in human lymphoma cell line T2 cells].

OBJECTIVE: To investigate the methylation of CpG island in the SHP-1 gene promoter and its significance in lymphoma. To evaluate the effects of As2O3 on demethylation of SHP-1 in human lymphoma cell line T2 and on proliferation of T2 cells. METHODS: T2 cells were treated with AsO3. Methylation specific PCR was used to detected the status of SHP-1 methylation in newly diagnosed lymphoma tissues and the T2 cells. The mRNA and protein expression of SHP-1 were determined by FQ-PCR and Western blot. The expression of phospha-c-kit was examined by Westren blot. MTT and flow cytometry were used to determine the growth and apoptosis in T2 cells. RESULTS: T2 cells contained completely methylated SHP-1. Furthermore, there was constitutive c-kit phosphorylation. The expression of SHP-1 was recoverd when the cells exposed to AsO3, and concomitant with increasing SHP-1, a parallel down-regulation of phosphorylated c-kit occurred, so that by day 3 phosphorylated c-kit was barely detectable. As2O3 inhibited the cell growth, and the effects were dose- and time-dependent. As2O3 also increased apoptosis rate of T2 cells in a dose- and time-dependent manner, too, and on the 1, 2, 3 d treatment with AsO3 (2.5 micromol/L), the apoptosis rates were 6.12%, 26.53%, 50.90%, respectively. The frequency of methylation in SHP-1 gene promoter in lymphoma tissues was 87.5% (28/32). In the control group, however, 12 specimens of benign lymph node proliferation showed no methylation in CpG island of SHP-1 gene promoter. CONCLUSION: Hypermethylation of SHP-1 gene promoter in lymphoma indicates the inactivation of SHP-1 gene and its possible role in the tumorigenesis of lymphoma. As2O3 can effectively cause demethylation and inhibit the growth of tumor by reactivating the SHP-1 gene transcription. SHP-1 methylation leading to epigenetic activation of c-kit may have a tentative role in the pathogenesis of lymphoma. Therefore, As2O3 is potentially useful in the treatment of lymphoma as a demethylating agent.

[The mechanism for SHIP gene to induce the apoptosis of human leukemia cell line K562.].

The src homology 2 (SH2)-domain containing inositol-5-phosphatase (SHIP) is another recently identified lipid phosphatase after phosphatase and tensin homology deleted on chromosome ten gene (PTEN). It plays an important role in negatively regulating the proliferation of hematopoietic cells. The relationship between SHIP and the inhibition of tumor proliferation is rarely reported. The purpose of this study is to evaluate the apoptosis induced by SHIP gene in K562 cell line and to explore the involved signaling pathway. The K562 cells were transfected with human SHIP gene by using the lentiviral vector containing SHIP, and the transfection was verified by fluorescent quantitative PCR (FQ-PCR) and Western blot. Then the effects of SHIP protein expression on cell growth and apoptosis were measured. The levels of p-Akt, bcl-2 family, caspase and the activity of NFkappaB were assayed by Western blot and ELISA, respectively. The results are as follows: (1) Human leukemia cell line K562 was SHIP-negative; (2) Transfection with SHIP gene led to the re-expression of SHIP mRNA and protein in K562, as shown by FQ-PCR and Western blot; (3) The expression of SHIP protein inhibited cell growth and significantly increased apoptosis in K562 cells; (4) Compared to that in control group, the expression level of p-Akt-308 and p-Akt-473 in SHIP-expressing cell group decreased significantly (P<0.01); SHIP activated caspase-9, caspase-3, up-regulated protein levels of bad, p27, down-regulated expression of bcl-xL, while it had no effect on the expression of bcl-2 and bax. Furthermore, the inhibition of NF-kappaB was achieved along with the inactivation of Akt. These data suggest that SHIP gene has potential abilities to inhibit K562 leukemic cell proliferation and induce its apoptosis via inactivating PI3K/Akt pathway. The loss of SHIP might be the explanation of aberrant high-level p-Akt in human leukemia. It may be at least one of the mechanisms by which the loss of SHIP expression contributes to leukemia progression.

Relative hematopoietic stem cell transplantation for the treatment of blastic plasmacytoid dendritic cell neoplasm: a case report and literature review.

OBJECTIVE: To report the long-term survival of a patient with maternal plasmacytoid dendritic cell tumor (BPDCN) treated by allo-HSCT. METHODS: The patient was diagnosed by skin infiltration, bone marrow involvement, skin biopsy and bone marrow cytology. CD4, CD56, and CR123 were expressed in tumor cells. The first complete remission (CR1) was achieved by CHOP-E and MA regimens before transplantation. In March 2018, HLA 5/10 matched hematopoietic stem cell transplantations were performed in the paternal donors and fathers. The pretreatment regimen was FTBI (4 Gy × 2, total lung dose 6 Gy) + CY (cyclophosphamide 1.8 g/m2 × 2 d) + Flu (30 mg/m2 × 4 d) + ATG (10 mg/kg); CSA + MMF + MTX to prevent GVHD. MNC 6.45 × 108/kg and CD34 + cells 7.40 × 106/kg were transfused back. + Granulocyte and platelet were engrafted 12 days and 14 days respectively. The donor-recipient chimerism was monitored regularly, immunosuppressive agents were regulated, and minimal residual disease (MRD) was monitored by flow cytometry. No DLI. RESULTS: Complete donor implantation and continuous remission were achieved after transplantation. After transplantation, complications such as mucositis, viral infection, hypoproteinemia, and renal dysfunction occurred. At present, the disease-free survival is 10 months. CONCLUSION: BPDCN combined with TBI in the CR1 phase can effectively control the disease; HLA haploidentical hematopoietic stem cell transplantation is also an alternative treatment, and complications should be treated in a timely manner.

T cell acute lymphoblastic lymphoma complicated with myeloid sarcoma in an adult: A case report.

The present case report describes a rare case of T cell acute lymphoblastic lymphoma (T-LBL) in the lymph node with myeloid sarcoma in the pericardium. A 33-year-old Chinese male was admitted to hospital on 4 July 2015 exhibiting a fever and having experienced wheezing and fatigue for the previous 7 days. Routine pathological, computed tomographic, cytological and immunophenotypic observations revealed a diagnosis of T-LBL in the lymph node on 7 August 2015, without evidence of bone marrow (BM) involvement. The patient received induction chemotherapy for T-LBL and achieved partial remission. The patient was identified to have multiple serous effusion and analysis of pericardial effusion cells revealed the diagnosis of T-LBL with extramedullary myeloid sarcoma (without BM involvement) on 25 November 2015. On 30 December 2015, the patient was identified to exhibit proliferation of primary myeloid cells in the peripheral blood and BM, and an abnormal karyotype in BM cells, indicating that the complicated myeloid sarcoma involved the BM. No matched donor was available so the patient received chemotherapy to manage the disease. The patient was discharged on 31 January 2016 and ceased treatment. The patient succumbed on 19 February 2016 at home. To the best of our knowledge, T-LBL complicated with myeloid sarcoma had not been previously reported in Chinese adult male patients. In addition, the involvement of the BM and aberrant karyotype of the complicated myeloid sarcoma in the patient were rare.

[A case of spontaneous remission of acute myeloid leukemia with rare t（10;11）（q22;q23） rearrangement: case report and literatures review].

OBJECTIVE: To summarize a case of acute myeloid leukemia（AML） with severe infection and a rare translocation of t（10;11）（q22;q23）who got spontaneous remission. METHODS: The laboratorial examination results and clinical data in this case were summarized in couple with the light of published literatures. RESULTS: Like most of the spontaneous remission cases, severe infection happened to this case of AML patient, but the different point was that a rare translocation of t（10;11）（q22;q23）was disclosed in this patient. There were only 6 cases of this kind of translocation reported by the literatures up to now. This patient got spontaneous remission after the controlled infection without any chemotherapy. The rare translocation of t（10;11）（q22;q23）disappeared after he got remission. CONCLUSION: Spontaneous remission of acute leukemia was a rare phenomenon, the underlying mechanism was unclear, maybe due to the inflammatory factors triggered by infection, or the activated immune system by the infection, or even the role of gene mutation factors. Accumulating data might shed insight into this rare kind of disease.

[Imatinib is effective in a 12-month-old boy with chronic myelogenous leukemia: case report and literature review].

OBJECTIVE: To summarize the clinical characteristics of an infant with chronic myelogenous leukemia (CML) and the effects of imatinib on the case. METHOD: The clinical features of an infant with CML, who was treated with imatinib in the Norman Bethune International Peace Hospital at June 2009, were retrospectively analyzed and the reports in literature were reviewed. The 1-year-old boy suffered from recurrent low-degree fever and pallor. He had a moderate anemia, distended abdomen and marked splenomegaly. Bone marrow aspiration revealed CML in chronic phase)CP). The t (9; 22))q34; q11) could be detected and BCR-ABL (p210) was positive. The boy was diagnosed as CML-CP and treated with imatinib 100 mg per day. There were 10 related papers and more than 100 child CML patients were reported as retrieved from CNKI)from its establishment to August 2014) and Wanfang Database)from its establishment to August 2014) when "Child", " Chronic" and "Leukemia" were used as keywords. And there were 30 related papers including 400 cases from PubMed Database (from its establishment to August 2014) and one detailed report of an infant with CML was retrieved when "childhood" and "chronic myeloid leukemia" "imatinib" were used as keywords. The clinical effects of imatinib in infant CML cases were analyzed and summarized based on the literature. RESULT: The boy obtained a complete hematologic response (CHR) at the 6th week of diagnosis, a complete cytogenetic response (CCyR) at the 3rd month and a complete molecular response)CMR) at the 12th month without side effect. This boy grows very well and after a 62-month follow-up, his disease was stable. According to the domestic literature, 5 children CML cases aged 6 -12 years were treated with imatinib without side effects and got complete hematologic response (CHR) after 2-month-therapy. The dose, metabolic characteristics and clinical observation of imatinib can be found in foreign literature and imatinib showed good response with good tolerance in children with CML. Imatinib is regarded as the first line drug for children CML. But it may affect the development of the children. CONCLUSION: The children with CML-CP had a good response to imatinib, but more experience in the treatment of children with CML with iniatinib is needed.

Artesunate-enhanced apoptosis of human high-risk myelodysplastic cells induced by the DNA methyltransferase inhibitor decitabine.

The present study aimed to investigate whether artesunate (ART) could enhance the rate of apoptosis induced by decitabine (DAC) in the high-risk myelodysplastic syndrome (MDS) SKM-1 cell line, and examine the potential underlying mechanisms. The cytotoxicity and effect upon the apoptosis of ART and DAC in the SKM-1 cells was detected using the cell counting kit-8 assay and flow cytometry, respectively. The SKM-1 protein expression levels of activated caspase-3, -9 and -8, cleaved poly(ADP-ribose) polymerase and apoptosis-inducing factor (AIF) were measured by western blotting. The laser confocal microscope analysis revealed AIF transfer to the nucleus. The growth inhibition and apoptosis rates of the ART- and DAC-treated SKM-1 cells were significantly increased compared with those of the single agent-treated SKM-1 cells (P<0.05). In addition, ART and DAC induced caspase-dependent apoptosis, while ART, but not DAC, induced caspase-independent apoptosis via AIF transfer from the mitochondria to the nucleus. In addition, ART-DAC-induced cell death was not attenuated by the caspase-3/7 inhibitor, Ac-DEVD-CHO. The results of the present study suggested that the ART-DAC combination exhibited increased effectiveness compared with the single-agent therapy, in vitro. The ART-DAC combined therapy not only activated a caspase-dependent apoptotic pathway, but also a caspase-independent mitochondrial pathway.

[One Case of Multiple Myeloma with Central Never System Infiltration].

OBJECTIVE: To analyses and summarize a case of multiple myeloma with disseminated infiltration in central nervous system. METHODS: The results of laboratorial examination and clinical data were analyzed and compared in the light of published literatures. RESULTS: The headache and diplopia were caused by infiltration of multiple myeloma cells to the central nervous system. Unlike those reported in the literatures, this case was a rare case of disseminated infiltration inside the brain, and plasma cells were CD56+, this patient has not yet accepted any multiple myeloma-associated treatment as like that reported in the literatures. And different from cases reported, this patient showed a good response to the intrathecal chemotherapy. CONCLUSION: Whether this good response is due to a heterogeneity of MM or effect of treatment-associated drug is still to be decided.

[Expression and clinical significance of MMP-2 and MMP-9 in B acute lymphoblastic leukemia].

This study was purposed to investigate the expression and clinical significance of MMP-2 and MMP-9 in patients with B-acute lymphoblastic leukemia (B-ALL). The expression of MMP-2 and MMP-9 in bone marrow mononuclear cells of B-ALL patients and normal controls was detected by RT-PCR. The gelatinolytic activity was detected by zymography. The results showed that the expression of MMP-2 in de novo and relapsed B-ALL patients was markedly higher than that in normal controls (P < 0.05). The expression of MMP-9 in de novo and relapsed B-ALL patients was markedly lower than that in normal controls (P < 0.05). The expression of MMP-2 and MMP-9 in patients with extramedullary infiltration was significantly higher than that in patients without extramedullary infiltration. The incidence of extramedullary infiltration in patients with MMP-2/MMP-9 (+) was markedly higher than that in patients with MMP-2/MMP-9 (-). The expression of MMP-9 was markedly higher in high-risk patients than that in standard-risk patients (P < 0.05), but the expression of MMP-2 had no significant difference between the high-risk and standard-risk patients (P > 0.05). It is concluded that MMP-2 and MMP-9 may be secreted by B lymphoblasts and may involve in the extramedullary infiltration. MMP-9 may correlate with poor prognosis.