Myelodysplastic syndrome transformed into B-lineage acute lymphoblastic leukemia: A case report.

BACKGROUND: Myelodysplastic syndromes (MDSs) are a group of hematological diseases caused by expansion of an abnormal clone of hematopoietic stem cells. Primary MDS is a potentially premalignant clonal disorder that may progress to overt acute leukemia in 25%-50% of cases. However, most of these cases evolve into acute myeloid leukemia and rarely progress to acute lymphoblastic leukemia (ALL). Thus, transformation of MDS into B-cell ALL is rare. CASE SUMMARY: A 58-year-old man was admitted to the hospital for reduced blood cell counts. Based on all the test results and the World Health Organization diagnosis and classification, the patient was finally diagnosed with ring-shaped sideroblastic MDS with refractory hemocytopenia due to multilineage dysplasia. We used red blood cell transfusions and other symptomatic support treatments. After 4 years, the patient felt dizziness, fatigue, and night sweats. We improved bone marrow and peripheral blood and other related auxiliary examinations. He was eventually diagnosed with B-lineage acute lymphocytic leukemia (MDS transformation). CONCLUSION: The number of peripheral blood cells, type of MDS, proportion of primitive cells in bone marrow, and number and quality of karyotypes are all closely related to the conversion of MDS to ALL.

Retraction of "Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating microRNA-34a-5p/NOTCH1 signaling pathway".

[This retracts the article DOI: 10.1515/biol-2020-0025.].

A case report of lineage switch from T-cell acute leukemia to B-cell acute leukemia.

RATIONALE: ALL is the most common form of leukemia (75% to 80%), it is characterized by clonal expansion of the lymphoid blasts in bone marrow, blood, and other tissues, which can be divided into T lineage and B lineage. Although relapse of acute leukemia is common, a change of immunophenotype at relapse only occurs rarely. Some of these cases have been labeled "lineage switch". PATIENT CONCERNS: A 31-year-old man had multiple lymph nodes in the neck, and the lymph nodes on the right side adhered to the surrounding tissues. His lymphocytes ratio in blood was up to 86.3%. Flow cytometry of the bone marrow aspirate showed positive results for CD2, CD5, CD7, cCD3, TDT, CD4, CD8, and CD10, negative results for CD34, CD117, CD33, HLA-DR, CD19, and CD20. Twenty six months later, the patient felt pain in the neck and shoulder after touching. His lymphocytes of blood were 109.9×109 /L. 43 fusion genes and positive BCR/ABL was detected. Flow cytometry of the bone marrow aspirate showed pro B lymphocytes accounted for 85.54%, and positive expression of CD38, CD10, CD34, CD33, TDT, CD9, and HLA-DR. Moreover, the RT-PCR data showed the patient expressed high level of T cell and B cell development transcription factors. DIAGNOSES: Upon examination, the patient was initially diagnosed with T-lineage pro cell ALL. BM morphologic analysis presented complete remission (CR) after systemic chemotherapy. Twenty six months later, we discovered the patient was diagnosed with B-lineage acute lymphocytic leukemia. INTERVENTIONS: Systemic chemotherapy is first given when a patient was diagnosed with T-cell acute lymphoblastic leukemia. After the patient happened linage switch, we adjusted the treatment plan, and the patient was complete remission after 1 course of treatment. OUTCOMES: Our case provides information of lineage switch from T-ALL to B-ALL in this report, which is never seen in our knowledge. LESSONS: This lineage switch from T-ALL to B-ALL is never reported beforemoreover, the RT-PCR data showed the patient expressed high level of T cell and B cell development transcription factors. Its early recognition can let doctor provides appropriate therapy to patient.

Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathway.

Multiple myeloma (MM) is a serious health issue in hematological malignancies. Long non-coding RNA taurine-upregulated gene 1 (TUG1) has been reported to be highly expressed in the plasma of MM patients. However, the functions of TUG1 in MM tumorigenesis along with related molecular basis are still undefined. In this study, increased TUG1 and decreased microRNA-34a-5p (miR-34a-5p) levels in MM tissues and cells were measured by the real-time quantitative polymerase reaction assay. The expression of relative proteins was determined by the Western blot assay. TUG1 knockdown suppressed cell viability, induced cell cycle arrest and cell apoptosis in MM cells, as shown by Cell Counting Kit-8 and flow cytometry assays. Bioinformatics analysis, luciferase reporter assay, and RNA pull-down assay indicated that miR-34a-5p was a target of TUG1 and directly bound to notch receptor 1 (NOTCH1), and TUG1 regulated the NOTCH1 expression by targeting miR-34a-5p. The functions of miR-34a-5p were abrogated by TUG1 upregulation. Moreover, TUG1 loss impeded MM xenograft tumor growth in vivo by upregulating miR-34a-5p and downregulating NOTCH1. Furthermore, TUG1 depletion inhibited the expression of Hes-1, Survivin, and Bcl-2 protein in MM cells and xenograft tumors. TUG1 knockdown inhibited MM tumorigenesis by regulating the miR-34a-5p/NOTCH1 signaling pathway in vitro and in vivo, deepening our understanding of the TUG1 function in MM.

A prospective, multicenter study of low dose decitabine in adult patients with refractory immune thrombocytopenia.

We conducted a prospective, multicenter study to evaluate the efficacy and safety of low-dose decitabine in adult patients with refractory immune thrombocytopenia. Adult patients who did not respond to, did not tolerate, or were unwilling to undergo splenectomy, with either a baseline platelet count less than 30 × 109 /L or the presence of bleeding symptoms and further need of ITP-specific treatments, were enrolled. Patients received decitabine at 3.5 mg/m2 intravenously for three consecutive days per cycle, for three cycles with a four-week interval between cycles. All patients were assessed every week during the first 12 weeks and at four-week intervals thereafter. We screened 49 patients for eligibility. Four patients were excluded and 45 received decitabine. At the end of decitabine treatment, complete response was achieved in eight patients (17.78%), and partial response was achieved in 15 patients (33.33%). The median time to initial response was 28 days (range, 14-70 days). Furthermore, seven relapsed patients received decitabine retreatment and all showed platelet response, including one complete response and six partial responses. Sustained response rates at 6, 12 and 18 months were 44.44% (20/45), 31.11% (14/45) and 20.0% (9/45), respectively. For responders, immune thrombocytopenia-related symptoms, fatigue, psychological health, fear, and overall quality of life were significantly improved. Adverse events were observed in 13 (28.89%) patients. No serious adverse events were recorded. In conclusion, low dose decitabine is potentially effective and safe in the management of adults with refractory immune thrombocytopenia. This trial is registered with clinicaltrials.gov identifier: NCT01568333.

Tumor necrosis factor receptor 2 may promote the proliferation and drug resistance of Kapras299 and L428 lymphoma cells via the AKT and WNT/ß-catenin signaling pathways.

Circulating soluble tumor necrosis factor receptor 2 (sTNFR2) has been associated with a relatively poor prognosis in various types of lymphoma. However, the specific role of TNFR2 expression in lymphoma cells remains uncharacterized. In the present study, TNFR2 expression was quantified in the Hodgkin lymphoma cell line, L428, and the anaplastic large-cell lymphoma cell line, Karpas299, using RT-PCR and western blot analyses. Karpas299 cells exhibited higher TNFR2 expression than L428 cells. Proliferation and drug resistance experiments demonstrated that Karpas299 cells also possessed a greater proliferative ability and resistance to adriamycin (ADM) than L428 cells, with 50% inhibitory concentrations (IC50) of 1.423±0.24 µmol/l for Karpas299 cells, compared with 0.728±0.15 µmol/l for L428 cells (P<0.05). The knockdown of TNFR2 in Karpas299 cells significantly reduced their proliferative ability; when treated with ADM, the cell inhibition rate increased from 49.34±5.42% to 74.13±6.81% (P<0.05). The upregulation of TNFR2 in L428 cells significantly increased their proliferative ability; when treated with ADM, the cell inhibition rate decreased from 47.03±5.25% to 28.71±4.90% (P<0.05). Investigation of the underlying molecular mechanism indicated that the upregulation of TNFR2 expression in L428 cells increased the expression of ß-catenin and the phosphorylation of AKT. In L428 cells overexpressing TNFR2, the ß-catenin blocker, DKK1, or the AKT inhibitor, LY294002, abrogated the increase in proliferation induced by TNFR2 and increased cell inhibition rate upon treatment with ADM. In summary, the present study demonstrated that TNFR2 promoted the proliferative and drug resistance abilities of lymphoma cells via the AKT and WNT/ß-catenin signaling pathways. This may provide the experimental basis for the further study of TNFR2 activity in lymphoma cells and warrant its investigation as a therapeutic target for lymphoma.

Telomere length is positively associated with the expression of IL­6 and MIP­1α in bone marrow mesenchymal stem cells of multiple myeloma.

Potential roles of mesenchymal stem cells (MSCs) in the pathogenesis of multiple myeloma (MM) are largely unknown. In the current study, the authors analyzed telomere length and the expressions of interleukin (IL)­6 and macrophage inflammatory protein (MIP)­1α in MSCs derived from the bone marrow (BM) of MM patients and controls. The current results demonstrated that there was no significant difference in cell surface expression of CD73 and CD90, and the capacity to differentiate into bone tissue were identified between the BM MSCs derived from MM patients and controls. Interestingly, telomere length (TL) and mRNA expressions of IL­6 and MIP­1α were significantly longer or higher in BM MSCs of MM than those of controls. Moreover, TL is positively associated with the expressions of IL­6 and MIP­1α at the mRNA level in BM MSCs of MM. Additionally, IL­6 and MIP­1α expression were significantly upregulated when MSCs from MM patients were cultured in the myeloma associated condition medium. The present study indicated that myeloma­associated elongation of TL of BM MSCs may be a key element contributing to the increased IL­6 and MIP­1α expression, by which MSCs in the tumor microenvironment may facilitate MM and/or MM bone disease development.