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Frontiers in Immunology 2023TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can either induce cell death or activate survival pathways after binding to death...
TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype and is associated with increased survival in cancer patients with high tumor macrophage content.
BACKGROUND
TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can either induce cell death or activate survival pathways after binding to death receptors (DRs) DR4 or DR5. TRAIL is investigated as a therapeutic agent in clinical trials due to its selective toxicity to transformed cells. Macrophages can be polarized into pro-inflammatory/tumor-fighting M1 macrophages or anti-inflammatory/tumor-supportive M2 macrophages and an imbalance between M1 and M2 macrophages can promote diseases. Therefore, identifying modulators that regulate macrophage polarization is important to design effective macrophage-targeted immunotherapies. The impact of TRAIL on macrophage polarization is not known.
METHODS
Primary human monocyte-derived macrophages were pre-treated with either TRAIL or with DR4 or DR5-specific ligands and then polarized into M1, M2a, or M2c phenotypes . The expression of M1 and M2 markers in macrophage subtypes was analyzed by RNA sequencing, qPCR, ELISA, and flow cytometry. Furthermore, the cytotoxicity of the macrophages against U937 AML tumor targets was assessed by flow cytometry. TCGA datasets were also analyzed to correlate TRAIL with M1/M2 markers, and the overall survival of cancer patients.
RESULTS
TRAIL increased the expression of M1 markers at both mRNA and protein levels while decreasing the expression of M2 markers at the mRNA level in human macrophages. TRAIL also shifted M2 macrophages towards an M1 phenotype. Our data showed that both DR4 and DR5 death receptors play a role in macrophage polarization. Furthermore, TRAIL enhanced the cytotoxicity of macrophages against the AML cancer cells . Finally, TRAIL expression was positively correlated with increased expression of M1 markers in the tumors from ovarian and sarcoma cancer patients and longer overall survival in cases with high, but not low, tumor macrophage content.
CONCLUSIONS
TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype via both DR4 and DR5. Our study defines TRAIL as a new regulator of macrophage polarization and suggests that targeting DRs can enhance the anti-tumorigenic response of macrophages in the tumor microenvironment by increasing M1 polarization.
Topics: Humans; TNF-Related Apoptosis-Inducing Ligand; Macrophages; Phenotype; RNA, Messenger; Receptors, Death Domain; Leukemia, Myeloid, Acute; Tumor Microenvironment
PubMed: 37809073
DOI: 10.3389/fimmu.2023.1209249 -
World Journal of Clinical Cases Sep 2023The mixed lineage leukemia (MLL)-eleven-nineteen lysine-rich leukemia (ELL) fusion gene is a rare occurrence among the various MLL fusion genes. We present the first...
BACKGROUND
The mixed lineage leukemia (MLL)-eleven-nineteen lysine-rich leukemia (ELL) fusion gene is a rare occurrence among the various MLL fusion genes. We present the first case in which myeloid sarcoma (MS) was the only manifestation of adult MLL-ELL-positive acute myeloid leukemia (AML).
CASE SUMMARY
We report a case of a 33-year-old male patient who was admitted in June 2022 with a right occipital area mass measuring approximately 7 cm × 8 cm. Blood work was normal. The patient underwent right occipital giant subscalp mass excision and incisional flap grafting. Immunohistochemistry was positive for myeloperoxidase, CD43 and CD45 and negative for CD3, CD20, CD34, and CD56. The bone marrow aspirate showed hypercellularity with 20% myeloblasts. Flow cytometry showed that myeloblasts accounted for 27.21% of the nucleated cells, which expressed CD33, CD38, and CD117. The karyotype was 46, XY, (11, 19) (q23; p13.1), -12, + mar/46, XY. Next-generation sequencing showed a fusion of MLL exon 7 to exon 2 of ELL. A diagnosis of MLL-ELL-positive AML (M2 subtype) with subcutaneous MS was made.
CONCLUSION
MLL-ELL-positive AML with MS is a rare clinical entity. Additional research is needed to elucidate the molecular mechanisms of the pathogenesis of MS.
PubMed: 37727473
DOI: 10.12998/wjcc.v11.i25.6000 -
International Journal of Hematology Dec 2023Myeloid sarcoma is a rare clinical entity that presents as an isolated proliferation of leukemic cells, concurrently with or at relapse of acute myeloid leukemia (AML),... (Review)
Review
Myeloid sarcoma is a rare clinical entity that presents as an isolated proliferation of leukemic cells, concurrently with or at relapse of acute myeloid leukemia (AML), myelodysplastic syndromes/neoplasms (MDS), chronic myeloid leukemia (CML), and myeloproliferative neoplasm (MPN). Myeloid sarcoma disrupts the normal architecture of its surrounding tissues. When it forms in long bones, it can cause their pathological fracture. We recently experienced a rare case of MDS presenting with myeloid sarcoma in the femur that eventually resulted in its pathological fracture. Detailed chromosomal analysis of the bone marrow cells suggested emergence of myeloid sarcoma during the fast-paced progression of MDS just after acquiring trisomy 22. A comprehensive review of previous cases of myeloid sarcoma-associated pathological fracture indicated possible involvement of structural rearrangements of chromosomes 9 and 22. Management of myeloid sarcoma should continue to improve, and clinicians should note that myeloid sarcoma with specific chromosomal alterations needs extra medical attention to prevent pathological fracture.
Topics: Humans; Sarcoma, Myeloid; Fractures, Spontaneous; Myeloproliferative Disorders; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute
PubMed: 37707761
DOI: 10.1007/s12185-023-03656-1 -
ACG Case Reports Journal Sep 2023Most gastric cancers are adenocarcinomas, but other malignancies can arise in the stomach. Patients with leukemia may develop myeloid sarcoma (MS) in the...
Most gastric cancers are adenocarcinomas, but other malignancies can arise in the stomach. Patients with leukemia may develop myeloid sarcoma (MS) in the gastrointestinal tract. Our patient was a 68-year-old woman who was initially diagnosed with acute myeloid leukemia and underwent a matched unrelated stem cell transplantation. She was in remission for 10 years before developing a rare case of gastric MS without acute myeloid leukemia. She had partial response to chemotherapy but ultimately died because of infection. Gastric MS has an incidence of less than 1%. Gastrointestinal involvement usually involves the small intestine and rarely the stomach.
PubMed: 37674880
DOI: 10.14309/crj.0000000000001137 -
Neurology India 2023
Topics: Humans; Sarcoma, Myeloid; Leukemia, Myeloid, Acute; Hematoma; Leukemia
PubMed: 37635551
DOI: 10.4103/0028-3886.383815 -
Journal of Surgical Case Reports Aug 2023Myeloid sarcoma (MS) is an extramedullary tumor mass causing proliferation of mature or immature blast cells of one or more myeloid lineages. Involvement of the...
Myeloid sarcoma (MS) is an extramedullary tumor mass causing proliferation of mature or immature blast cells of one or more myeloid lineages. Involvement of the genitourinary tract is rare. We present a case of MS of the ureteral wall. A 74-year-old man was evaluated for left hydronephrosis and ipsilateral low back pain. A computed tomography scan showed a nodular formation in the pelvic ureter. Urinary cytology revealed cellular atypia, so ureteroscopy was performed showing a distal ureteral mass. The histological examination of the biopsy revealed to be malignant neoplasm. The patient underwent left laparoscopic nephroureterectomy with bladder cuff excision. Microscopic histological examination revealed a tumor compatible with MS. A postoperative positron emission tomography revealed residual hypercaptation of the bladder, pelvic muscle and iliac nodes, so the patient started chemotherapy. A multidisciplinary approach was required, taking into account the patient's age, the already poor renal function and the location of the neoplasm.
PubMed: 37614469
DOI: 10.1093/jscr/rjad433 -
Clinical Case Reports Aug 2023This is the first case of a promyelocytic sarcoma diagnosed on pleural effusion and exposed the difficulty of demonstrating a leukemic phase in patients with bone...
KEY CLINICAL MESSAGE
This is the first case of a promyelocytic sarcoma diagnosed on pleural effusion and exposed the difficulty of demonstrating a leukemic phase in patients with bone diseases, such as Gorham's disease. It also showed that promyelocytic sarcoma can be treated by ATRA/ATO-based therapy with an efficient and tolerated response.
ABSTRACT
Myeloid sarcoma (MS) is a rare extramedullary tumoral infiltration of immature myeloid cells and can occur in different sites of the body, without leukemic infiltration. A 38-year-old woman patient presented at emergency with a pleural effusion, bicytopenias, and Gorham's disease, a very rare bone disorder. In the following days, she worsened with a chylothorax and pancytopenias. Pleural puncture cytologically revealed promyelocytes with Auer rods. Cytogenetic and molecular analyses subsequently confirmed the presence of the t(15:17) translocation. However, no circulating phase of these atypical promyelocytes was found. Similarly, no other origin was identified. We conclude that the patient had a MS of unknown etiology in the form of a pleural effusion with pathological promyelocytes. The patient was treated with a combination of oral all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) with a cytological and molecular remission persisting 3 months after diagnosis. We report here the first case of a promyelocytic MS of pleural origin without concomitant evidence of acute promyelocytic leukemia. We also show the efficacy of ATRA/ATO treatment in this etiology.
PubMed: 37601428
DOI: 10.1002/ccr3.7785 -
Frontiers in Pharmacology 2023Treatment of relapsed or refractory acute myeloid leukemia (R/R AML) and myeloid sarcoma (MS) has presented challenges for decades. Studies on selinexor in combination...
Real-world experience with selinexor-containing chemotherapy-free or low-dose chemotherapy regimens for patients with relapsed/refractory acute myeloid leukemia and myeloid sarcoma.
Treatment of relapsed or refractory acute myeloid leukemia (R/R AML) and myeloid sarcoma (MS) has presented challenges for decades. Studies on selinexor in combination with various standard or intensive chemotherapy regimens for the treatment of R/R AML have demonstrated promising results. This study aimed to evaluate the efficacy and safety of chemotherapy-free or low-dose chemotherapy regimens with selinexor for R/R AML and MS patients. Ten patients with R/R AML or MS who received chemotherapy-free or low-dose chemotherapy regimens in combination with selinexor at Tongji Hospital from October 2021 to August 2022 were included in this study. The primary endpoint was overall response rate (ORR) and secondary endpoints included complete remission (CR), CR with incomplete hematological recovery (CRi), partial remission (PR), transplantation rate, and safety. All patients were evaluable for response, achieving CR in four (40.0%) patients and CRi in two (20.0%) patients for a total CR/CRi of 60.0%. The ORR was 80.0% when patients with PR were included. Five (50.0%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after treatment with selinexor-containing regimens. At the end of the follow-up, seven (70.0%) patients were alive, and three patients died of transplant-related complications or disease progression. The most frequently reported nonhematologic adverse events (AEs) in patients were grade 1 or 2 asymptomatic hyponatremia. The chemotherapy-free or low-dose chemotherapy regimens in combination with selinexor for R/R AML are feasible and tolerable and provide an opportunity for patients to receive transplantation.
PubMed: 37601075
DOI: 10.3389/fphar.2023.1217701 -
Cancers Aug 2023Hematological neoplasms sharing a blastic morphology may involve the skin. The skin may be either the primary site of occurrence of hematological malignancies with... (Review)
Review
Hematological neoplasms sharing a blastic morphology may involve the skin. The skin may be either the primary site of occurrence of hematological malignancies with blastic features or cutaneous lesions are the first manifestation of an underlying systemic malignancy. The assessment of skin biopsies of hematological neoplasms with blastic features poses diagnostic problems and requires expert hematopathologists considering a wide range of differential diagnoses. The precise diagnosis of diseases sharing blastic features but with different outcomes and requiring distinct therapies is essential for patient management. The present paper mainly focuses on cutaneous involvement of the blastoid variant of mantle cell lymphoma and lymphoblastic lymphoma of B-cell or T-cell origin. The relevant literature has been reviewed and the clinical aspects, pathological features, prognosis, and therapy of both blastoid mantle cell lymphoma and lymphoblastic lymphoma involving the skin are discussed. A focus on other hematological entities with blastic features, which may involve the skin, to be taken into consideration in differential diagnosis is also given.
PubMed: 37568745
DOI: 10.3390/cancers15153928