Search

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 Myc antagonists Mad1, Mxi1 and Rox proteins share two highly conserved domains, Sin3-interacting domain (SID) and basic helix-loop-helix leucine zipper domain (bHLHzip), which are essential for these proteins to function during molecular switching from proliferation to differentiation. In an attempt to identify mutations in Mad1, Mxi1 and Rox genes in human haematological malignancies, we screened 10 haematopoietic cell lines, bone marrow mononuclear cells (BMMNC) from 26 patients with haematological malignancies and peripheral blood mononuclear cells (PBMNC) from 30 healthy volunteers, using reverse transcription-polymerase chain reaction, single strand conformation polymorphism analysis and sequencing. Mad1, Mxi1 and Rox genes were expressed in all samples. Four polymorphisms were found in cell lines BMMNC and PBMNC: two in Mad1, one in Mxi1 and one in Rox. Nine missense mutations were detected: two in Mad1 in patients, four in Mxi1 (three in patients and one in KG-1 cell line), and three in Rox in patients. No mutations were detected in PBMNC from healthy volunteers. Among six patients with acute lymphoblastic leukaemia, two had Mxi1 mutations and another two had Rox mutations. These mutations were associated with poorer clinical outcomes. This is the first report to show that Mad1, Mxi1 and Rox genes were expressed and displayed mutations in haematological malignancies.

This study was purposed to investigate the expression and methylation status of TIG1 in acute leukemia (AL). The TIG1 expression of 53 cases of AL and 20 cases of normal control (NC) were measured by using real-time quantitative PCR (RT-QT-PCR) and methylation-specific PCR(MS-PCR). The leukemia KG-1a, U937 and K562 cells were treated with 5-Aza-CdR. The results indicated that TIG1 gene expressed at a high level in cases of NC, but expressed at a low level in patients with AL. TIG1 gene was unmethylated in NC, but frequently methylated in AL. Aberrant methylation rate of TIG1 in AL was 75% (40/53). The expression of TIG1 in unmethylated patients was higher than that in methylated patients. Hypermethylation of TIG1 promoter CpG islands was detected in all the cell lines. 5-Aza-CdR treatment led to the hypomethylation of TIG1 promoter CpG islands. After the treatment with 5-Aza-CdR of different concentration, the expression of TIG1 was restored, and the effect of 5-Aza-CdR displayed dose-dependency. It is concluded that the reduced expression of TIG1 may play an important role in the pathogenesis of AL, and methylation may be responsible for the decreased transcription of TIG1 gene.

In order to enhance the understanding of thrombotic thrombocytopenic purpura (TTP), the clinical features, laboratory characteristics, treatment and outcome of 14 patients with TTP were retrospectively analyzed and investigated. The results showed that 7 out of 14 patients with TTP had predisposing factors, such as pregnancy in 4 cases, infection in 3 cases, systemic lupus erythematosus (SLE) in 1 case and hematopoietic stem cell transplantation (HSCT) in 1 case. Fourteen patients all had neuropsychological symptoms, hemolytic anemia with negative-Coombs test, and decreased platelet counts. Eight patients had irregular fever with different degree. There were 8 patients with kidney damage including proteinuria in 8 cases and renal function abnormalities in 4 cases. The von Willebrand factor-cleaving protease (VWF-CP, ADAMTS13) activity of 13 cases out of 14 patients significantly decreased (less than 10%). At same time, plasma ADAMTS13 inhibitors were detected in 12 cases out of these 13 patients with decreased ADAMTS13 activity. After treatment with plasma exchange, glucocorticoid and rituximab so on, 12 cases achieved complete remission, in which 8 cases relapsed in two years. Two patients died at last, in which one case was secondary to HSCT. It is concluded that TTP is a kind of thrombotic microangiopathy due to platelet microthrombosis involved in multiple systems and multiple organs dysfunction with dangerous clinical process. The mortality of TTP patients is very high. Early diagnosis and early treatment with plasma exchange as the main means can greatly improve the prognosis of patients with TTP.

To investigate the expression and mutation of Mad1, Mxi1 and Rox genes in leukemia cells.Expression and mutation of Mad1, Mxi1 and Rox genes in bone marrow mononuclear cells (BMMNC) from 26 de novo acute leukemia (AL) patients, and in peripheral blood mononuclear cells (PBMNC) from 30 healthy volunteers, as well as in 7 human leukemic cell lines were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), single strand conformational polymorphism (SSCP) and DNA sequencing.RT-PCR showed that all the above cells expressed Mad1, Mxi1 and Rox mRNA. SSCP revealed four polymorphisms: two in Mad1, one each in Mxi1 and Rox. DNA sequencing detected nine missense mutations: two in Mad1 in AL patients, four in Mxi1 (three in AL patients and one in KG-1 cell line), and three in Rox in AL patients. The mutations of Mad1, Mxi1 and Rox mRNA were detected in 2, 3 and 3 patients, respectively.It is for the first time to demonstrate the mutations of Mad1, Mxi1 and Rox genes in AL patients suggesting these mutated genes involve in the pathogenesis of leukemia.

Previous studies demonstrated that interleukin-12 (IL-12) enhances the non-MHC-restricted cytotoxic activity of NK cells and facilitate specific allogeneic human cytotoxic T lymphocyte responses against fresh leukemia cells and cell lines. The Wilms' tumor gene, WT1 mRNA, has been used as a marker of minimal residual disease (MRD) for evaluating therapeutic efficacy of patients with leukemia or myelodysplastic syndrome (MDS). This study was aimed to investigate whether in vitro IL-12 can lower WT1 gene expression in peripheral blood monuclear cells (PBMNC) from patients with leukemia or MDS. PBMNC from these 30 patients and 5 healthy volunteers were cultured at 5 x 10(5) cells/ml alone with or without 100 units/ml of IL-12 for 3 days. WT1 mRNA was measured by competitive reverse transcription polymerase chain reaction (RT-PCR) since WT1 mRNA is considered as a marker of minimal residual disease (MRD) in leukemia and MDS. The results demonstrated that WT1 mRNA in PBMNC of 5 healthy volunteers was less than 10(3) copies/microg of total RNA. Following the 3-day IL-12 treatment, mean WT1 mRNA of PBMNC was reduced from 10(4.8) to 10(4.2) copies/microg of total RNA in 6 CML patients, from 10(5.4) to 10(4.8) copies/microg in 12 MDS patients and from 10(5.0) to 10(4.2) copies/microg in 5 AML patients in CR, but not reduced in 5 of 7 AML in non-CR. It is concluded that IL-12 significantly decrease the quantity of leukemia cells in PBMNC of most patients with MDS, CML and AML in CR. IL-12 may be of considerable benefit in the elimination of MRD in patients with hematological malignancies.