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Background: Myelodysplastic syndrome (MDS) features bone marrow failure and a heightened risk of evolving into acute myeloid leukemia (AML), increasing with age and reducing overall survival. Given the unfavorable outcomes of MDS, alternative treatments are necessary. Glutamine, the most abundant amino acid in the blood, is metabolized first by the enzyme glutaminase (GLS)., Objectives: To investigate whether GLS is involved in the progression of MDS. The efficacy of GLS inhibitors (CB839 or IPN60090) and BCL2 inhibitor venetoclax was also examined., Methods: We employed GLS inhibitors (CB839, IPN60090) and the BCL2 inhibitor venetoclax, prepared as detailed. MDS and AML cell lines were cultured under standard and modified (hypoxic, glutamine-free) conditions. Viability, proliferation, and caspase activity were assessed with commercial kits. RT-PCR quantified gene expression post-shRNA transfection. Mitochondrial potential, ATP levels, proteasome activity, and metabolic functions were evaluated using specific assays. Statistical analyses (t-tests, ANOVA) validated the findings., Results: The glutamine-free medium inhibited the growth of MDS cells. GLS1 expression was higher in AML cells than in normal control samples (GSE15061), whereas GLS2 expression was not. Treatment of MDS and AML cells for 72 h was inhibited in a dose-dependent manner by GLS inhibitors. Co-treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax and GLS inhibitors increased potency. Cells transfected with GLS1 short hairpin RNA showed suppressed proliferation under hypoxic conditions and increased sensitivity to venetoclax., Conclusions: Targeting glutaminolysis and BCL2 inhibition enhances the therapeutic efficacy and has been proposed as a novel strategy for treating high-risk MDS and AML.

Primary effusion lymphoma (PEL) is a large B-cell lymphoma that only proliferates proliferating effusion in the body cavity. It is associated with human herpesvirus 8 (HHV8).HHV8 negative effusion lymphoma, which is different from PEL in many ways, has also been reported and is referred to as HHV8-unrelated PEL-like lymphoma. This lymphoma is very rare and its clinical characteristics have not been fully clarified.A 79-year-old male developed HHV8-negative primary effusion lymphoma during treatment for myelodysplastic syndrome.Abdominal computed tomography revealed abdominal effusion, but did not show any evidence of a tumor mass or lymph node enlargement. A cytological analysis of his pleural effusion revealed atypical lymphoid cells that were negative for CD10, and positive for CD19 and CD20. Corticosteroids were administered to treat the abdominal effusion; however, the patient died of an exacerbation of lymphoma on the 20th day after the initiation of corticosteroid therapy. We herein report the case of an HIV seronegative elderly patient with HHV8-unrelated PEL-like lymphoma.

Myelodysplastic syndrome (MDS) is a group of clonal disorders affecting hematopoietic stem cells. Thus, the only potential curative therapy is hematopoietic stem cell transplantation (HSCT). Indeed, for high-risk patients with MDS, who have a higher anticipated risk of leukemic transformation and shorter survival, HSCT is the first choice for eligible patients. DNA hypomethylating agents, the only agents proved to prolong survival, are used in non-HSCT-eligible high-risk patients with MDS. In contrast, due to high transplant-related mortality rate, treatment strategies other than HSCT are mainly applied for the low-risk group with expected long-term survival. Lately, treatment options, including the progress of supportive therapy, for low-risk patients with MDS have increased. The availability of the treatment options that enhance QOL and prolong survival is the need of the present time. This review will discuss the outline of such treatment strategies, especially for low-risk patients with MDS.

Pleural effusion may occur as a rare complication associated with myeloid hematological malignancies. However, it occasionally occurs in patients with myelodysplastic/myeloproliferative neoplasms(MDS/MPN), especially in chronic myelomonocytic leukemia(CMML)with marked leukocytosis. Pleural effusion can also develop in hematological disorders with bone marrow fibrosis. Here, we report a case of CMML with bone marrow fibrosis, in which massive pleural effusion developed rapidly during cytoreductive therapy with hydroxycarbamide(HU). At the same time, the patient's leukocytosis was well controlled by the HU treatment. Although the cause of the patient's pleural effusion was unclear, despite a detailed thoracoscopic investigation, it is suspected that the invasion of leukemia cells or extramedullary hematopoiesis in the thoracic cavity may have led to this complication. Our findings suggest that in MPN and hematological disorders with bone marrow fibrosis, pleural effusion should be considered as a possible complication and should be carefully monitored, even when cytoreductive therapy is effective.

We report a patient with myelodysplastic syndrome (refractory anemia) showing the karyotype 46,XY,+1,der(1;10)(q10;p10), resulting in trisomy 1q and monosomy 10q abnormality. This finding suggests that either trisomy of 1q or centromeric connection between chromosomes 1 and 10, rather than the absence of 10q, might be essential toward neoplastic transformation.

Background: Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder defined by cytopenia and is associated with an increased risk of transformation to acute myeloid leukemia (AML). The outcome of MDS is poor, so alternative therapeutic approaches are needed to improve survival. The inhibition of the DNA damage response pathway, including poly (ADP-ribose) polymerase-1 (PARP-1), has been approved to treat several cancers. In addition, WEE1, a nuclear kinase, is overexpressed in many cancers. Therefore, a WEE1 inhibitor combined with a PARP-1 inhibitor could inhibit the proliferation of MDS and AML. Methods: We analyzed whether WEE1 was regulated in the progression of MDS and AML. We also evaluated the efficacy of MK-1775 (WEE1 inhibitor) and talazoparib (PARP-1 inhibitor). Results: PARP-1 expression was higher in the AML cells than in the MDS cells. However, WEE1 expression remained unchanged. MK-1775 or talazoparib alone inhibited MDS and AML cells after 72 h, and cellular cytotoxicity and caspase 3/7 activity were increased. The combined use of MK-1775 and talazoparib produced superior efficacy than either drug alone and SKM-1 colony formation was reduced. Significant cell populations in the sub-G1 phase were found in the cell-cycle analyses. Additionally, γ-H2AX expression and caspase 3 activity were increased. The combined treatment also changed the mitochondrial membrane potential. Conclusions: The combination of a WEE1 inhibitor and PARP-1 inhibitor had enhanced efficacy and is proposed as a new therapeutic option for patients with MDS or AML. Our findings have clinical implications for a potential novel therapeutic strategy for MDS and AML patients. [ABSTRACT FROM AUTHOR]

A case study is presented of a female patient diagnosed with aplastic anemia and also discusses the treatment of paroxysmal nocturnal hemoglobinuria (PNH) which is an acquired hematopoietic stem cell disorder. It informs that infections and surgical procedures can increase the complications of hemolysis for the patients of PNH.