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Acute Promyelocytic Leukemia - Crossref

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Last Updated: 04 September 2022

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Identification of IRF8 as a potent tumor suppressor in murine acute promyelocytic leukemia

Although the role of promyelocytic leukemia/retinoic acid receptor (u03b1 fusion protein) is well known in acute promyelocytic leukemia, advocative leukemia, is not fully understood, its contribution to the initiation and maintenance of leukemogenesis is uncertain. IRF8 has been linked to myeloid neoplasia in myeloid neoplasia, and mice lacking IRF8 develop a well-defined myeloproliferative neoplasm with increased neutrophilic lineage cells. We observed significant decrease in the IRF8 protein levels in PML/RARA transgenic mice populations. In addition, we found that missing IRF8 results in proliferation of promyelocytes in vivo, partially reproducing the effect of PML/RARA expression. In addition, survival studies revealed that complete absence of IRF8 leads to APL formation in our PML/RARA mice. These results reveal IRF8 downregulation as an important factor in APL establishment and highlight a tumor-suppressor role for IRF8 in this acute leukemia.

Source link: https://doi.org/10.1182/bloodadvances.2018018929


Concomitant central venous sinus thrombosis and subdural hematoma in acute promyelocytic leukemia: middle meningeal artery embolization enables safe anticoagulation. Illustrative case

BACKGROUND Acute promyelocytic leukemia has long been associated with coagulation disorders. OBSERVATIONS In this case, a 25-year-old female with newly diagnosed APL has extensive cerebral venous thrombosis and was started on a treatment with idarubicin and all-trans retinoic acid. The patient was started on a heparin drip, but her medical course was complicated by subdural hemorrhage and epidural hemorrhage in the setting of thrombocytopenia. The authors investigated middle meningeal artery embolization in order to resume anticoagulation for CVT with a small risk of SDH. LesSONS AMERICA embolization ensures safe anticoagulation in patients with concomitant CVT and SDH.

Source link: https://doi.org/10.3171/case2080


Granulocytic sarcoma: an unusual complication of acute promyelocytic leukemia causing cerebellar hemorrhage

GRANUCYTIC sarcomas, which occur mainly in patients with acute myelogenous leukemia or other myeloproliferative disorders, are rarely seen in patients with acute promyelocytic leukemia or other myeloproliferative disorders, and have never been reported in the cerebellum. In the cerebellum, the authors discuss the case of a patient with APL who had a hemorrhagic granulocytic sarcoma. APL was diagnosed by leukemic blast cells in bone marrow samples, and results from hematological tests led to a diagnosis of APL. The blast cells were positive for leukocyte common antigen CD13, and CD33 markers, according to flow cytometry. This is the first study to reveal granulocytic sarcoma in the cerebellum as the primary presentation in a patient with APL and abnormal coagulation. Although APL patients' central nervous system disorders are uncommon, the results in this instance show the importance of personalized therapy when such conditions occur.

Source link: https://doi.org/10.3171/jns.2006.105.6.912


Downregulation of hsa-miR-4328 and target gene prediction in Acute Promyelocytic Leukemia

Abstract : The PML-RARA fusion gene codes for acute promyelocytic leukemia. APL therapy can have significant side effects, so the research of effective therapeutic options is vital. MiRNAs can be used as potential biomarkers in APL and can be used as therapeutic targets or as indicators of therapeutic response. Objectives : The aim of this research was to determine whether differentially expressed putative miRNAs that have RARA as a target gene could be used as reliable biomarkers for APL. Methods : A panel of 6 miRNAs with potential tropism for the RARA gene was selected from miRDB using bioinformatics methods. Of the six miRNAs, hsa-mir-4328 is significantly reduced in APL-treated populations compared to healthy controls, but hsa-mir-4299 and hsa-mir-7851-3p show little differences in expression between the two study groups, but not in statistical significance.

Source link: https://doi.org/10.2478/rrlm-2022-0022


Targeting the SUMO pathway primes all- trans -retinoic acid-induced differentiation of non promyelocytic Acute Myeloid Leukemias

Abstract Differentiation therapies using All-transretinoic acid are particularly effective at treating Acute Promyelitis Leukemia, a minor subtype of Acute Myeloid Leukemia. In non-APL AML cells, controlledled inhibition of SUMOylation by pharmaceutical inhibitors, or overexpression of SENP desumoylases, are potently raising the ATRA-induced expression of key genes involved in differentiation, proliferation, and apoptosis. In conclusion, blocking the SUMO pathway can be a promising way to sensitize non-AML AML patients to retinoids and improve the diagnosis of this poor prognosis cancer, which has not significantly changed in the last 40 years.

Source link: https://doi.org/10.1101/254946


HSPA8 chaperone complex drives chaperone-mediated autophagy regulation in acute promyelocytic leukemia differentiation

Abstract Acute myeloid leukemia is a disease of the hematopoietic system that is characterized by the hyperproliferation of undifferentiated cells of the myeloid lineage. Although most of AML therapies are focusing on tumor debulking, all-trans retinoic acid induces differentiation in acute promeylocytic leukemia a specific subgroup. In addition, we used ATRA-responsive and u2013-resistant cells to further dissect a potential role for CMA in ATRA-mediated neutrophil differentiation. CMA-related mRNA transcripts are more present in immature hematopoietic cells than in neutrophils, according to this study. During ATRA-induced differentiation of APL cells, lysosomal degradation of the mCherry-KFERQ CMA reporter decreases. On the other hand, we found that macroautophagy flux primed the ATRA-resistant NB4-R1 cells to distinguish on ATRA therapy, but that reduced LAMP-2A and HSPA8 is required for complete neutrophil maturation.

Source link: https://doi.org/10.1101/2022.08.07.502745


Papilledema and idiopathic intracranial hypertension due to the possible potentiation of ATRA by posaconazole in a case of acute promyelocytic leukemia

Since the concomitant use of ATRA with azole group antimicrobials such as fluconazole and voriconazole, IIH infections have been recorded in IIH. We explore the diagnosis and treatment process of the IIH in a young acute promyelocytic leukemia case with the ATRA's ATRA effect, which can be boosted by posaconazole. On the 12th day of the AIDA protocol and posaconazole proflaxis, headache and blurred vision were induced. ATRA therapy was restarted without posaconazole, after widespread clinical response was found, but a similar clinical condition did not persist. Discussion The use of ATRA and azole group drugs in conjunction raises the risk of developing IIH. Patients with APL who developed IIH during the concomitant use of ATRA and fluconazole or voriconazole have been identified. Our case is the first APL case involving a IIH who underwent ATRA-based therapy and used posaconazole, to the best of our knowledge.

Source link: https://doi.org/10.1177/10781552221076756


Arsenic trioxide dose capping to decrease toxicity in the treatment of acute promyelocytic leukemia

ATO is dosed on actual body weight, and high ATO doses in overweight patients can increase toxicity. We conducted a retrospective, two-center study comparing toxicities in patients undergoing Lo-Coco's ATO, u226410 mg/dose, and non-capped ATO, > 10 mg/dose. During induction, there were no differences between grade u22653 hemotoxicity, grade u22653 QTc increase, neurotoxicity, and cardiac toxicity among groups; none of them received doses u226410 mg and 29 received > 10 mg.

Source link: https://doi.org/10.1177/10781552211024727


CD44–fibrinogen binding promotes bleeding in acute promyelocytic leukemia by in situ fibrin(ogen) deposition

Abstract The primary obstacle to the successful treatment of acute promyelocytic leukemia is early hemorrhagic disease. CD44 on the membrane of APL blasts and NB4 cells ligated bound fibrinogen, resulting in situ deposition of fibrin and abnormal fibrin distribution. In addition, CD44 expression in an APL mouse model was not limited to bleeding disorders alone, but it was also linked to the wound-healing process and the survival time of APL mice. Our results show that CD44 may be a potential intervention target for APL bleeding disorders.

Source link: https://doi.org/10.1182/bloodadvances.2022006980


The role of adjuvant chemotherapy in the management of acute promyelocytic leukemia differentiation syndrome

We conducted a three-institution retrospective review to determine the role of short-term adjuvant chemotherapy in treating moderate DS in patients with low- or intermediate-risk APLs that were initially treated with ATRA/ATO only protocols. We investigated the difference in the occurrence and duration of moderate DS in APL patients who were treated with ATRA/ATO with or without adjuvant chemotherapy with or without adjuvant chemotherapy. The study found and included 57 low- or intermediate-risk APL patients; 36 patients under ATRA/ATO only induction therapy; 21 patients received ATRA/ATO/adjuvant chemotherapy combination induction therapy; and 21 patients underwent ATRA/ATO/adjuvant chemotherapy mixture induction therapy; 36 patients were retrospectively identified and included; 36 patients under ATRA/ATO only induction therapy; and 21 patients received ATRA/ATO/adjuvant chemotherapy combination induction therapy Patients receiving ATRA/ATO for a month were expected to recover DS in patients receiving ATRA/ATO for 17 days, and in patients receiving combination therapy, it was 8 days. In conclusion, adding adjuvant chemotherapy to ATRA/ATO only protocol may reduce the duration of DS and hospital stay during APL induction therapy.

Source link: https://doi.org/10.3389/fonc.2022.911745

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions