Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous reports of leukemia in hedgehogs are limited. We describe clinicopathologic features of leukemia in 9 hedgehogs, including eosinophilic leukemia (n = 3) and acute leukemia/leukemic phase of lymphoma (n = 6). All 3 hedgehogs with eosinophilic leukemia were older than 2 years of age; in contrast, 4 of 6 cases of acute leukemia/lymphoma were <2 years old. Hedgehogs presented for non-specific clinical signs of anorexia and lethargy. On hematologic testing, hedgehogs with eosinophilic leukemia had a marked leukocytosis, consisting mostly of eosinophilic precursors with fewer mature eosinophils, whereas there were 43-97% immature cells (blasts) in the blood of hedgehogs with acute leukemia/lymphoma. Anemia (n = 6) and/or thrombocytopenia (n = 6) were concurrent findings. Increased liver enzyme activities (alanine aminotransferase, alkaline phosphatase) and hypoalbuminemia were the common findings on biochemical panels. All cases of eosinophilic leukemia and 4 cases of acute leukemia/lymphoma died shortly after diagnosis (median 7 days, range 0-41 days), whereas 2 cases of acute leukemia/lymphoma lived for 94 or 101 days. Postmortem examination in 5 cases (1 eosinophilic leukemia, 4 acute leukemia/lymphoma) showed bone marrow infiltrates, confirming eosinophilic leukemia and acute leukemia in 1 and 3 cases, and bone marrow necrosis in 1 animal with acute leukemia/lymphoma. Immunohistochemical staining of bone marrow sections confirmed a T-cell acute leukemia in 1 case. Several hedgehogs had concurrent carcinomas. Hedgehogs suffer from eosinophilic leukemia and acute leukemia/lymphoma. However, classification of acute leukemia by lineage was not possible due to lack of hedgehog cross-reactive or species-specific reagents.
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PMID:Clinicopathologic Findings of Spontaneous Leukemia in 9 Pet African Hedgehogs (Atelerix Albiventris). 3211 73

Aberrant activation of the hedgehog (HH) pathway is observed in many neoplasms, including acute myeloid leukemia (AML). The glioma-associated oncogene homolog (GLI) transcription factors are the main downstream effectors of the HH signaling cascade and are responsible for the proliferation and maintenance of leukemic stem cells, which support chemotherapy resistance and leukemia relapse. Cytarabine (Ara-C)-resistant variants of AML cell lines were established through long-term cultivation with successively increasing Ara-C concentrations. Subsequently, differences in GLI expression were analyzed by RT-qPCR. GLI3 mRNA levels were detectable in parental Kasumi-1, OCI-AML3, and OCI-AML5 cells, whereas GLI3 expression was completely silenced in all resistant counterparts. Therefore, we generated GLI3-knockdown cell lines using small hairpin RNAs (shRNA) and evaluated their sensitivity to Ara-C in vitro. The knockdown of GLI3 partly abolished the effect of Ara-C on colony formation and induction of apoptosis, indicating that GLI3 downregulation results in Ara-C resistance. Moreover, we analyzed the expression of several genes involved in Ara-C metabolism and transport. Knockdown of GLI3 resulted in the upregulation of SAM and HD domain-containing protein 1 (SAMHD1), cytidine deaminase (CDA), and ATP-binding cassette C11 (ABCC11)/multidrug resistance-associated protein 8 (MRP8), each of which has been identified as a predictive marker for Ara-C response in acute myeloid leukemia. Our results demonstrate that GLI3 downregulation is a potential mechanism to induce chemotherapy resistance in AML.
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PMID:Downregulation of GLI3 Expression Mediates Chemotherapy Resistance in Acute Myeloid Leukemia. 3270 52

Conventional therapy for acute myeloid leukemia is composed of remission induction with cytarabine- and anthracycline-containing regimens, followed by consolidation therapy, including allogeneic stem cell transplantation, to prolong remission. In recent years, there has been a significant shift toward the use of novel and effective, target-directed therapies, including inhibitors of mutant FMS-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase (IDH), the B-cell lymphoma 2 inhibitor venetoclax, and the hedgehog pathway inhibitor glasdegib. In older patients the combination of a hypomethylating agent or low-dose cytarabine, venetoclax achieved composite response rates that approximate those seen with standard induction regimens in similar populations, but with potentially less toxicity and early mortality. Preclinical data suggest synergy between venetoclax and FLT3- and IDH-targeted therapies, and doublets of venetoclax with inhibitors targeting these mutations have shown promising clinical activity in early stage trials. Triplet regimens involving the hypomethylating agent and venetoclax with FLT3 or IDH1/2 inhibitor, the TP53-modulating agent APR-246 and magrolimab, myeloid cell leukemia-1 inhibitors, or immune therapies such as CD123 antibody-drug conjugates and programmed cell death protein 1 inhibitors are currently being evaluated. It is hoped that such triplets, when applied in appropriate patient subsets, will further enhance remission rates, and more importantly remission durations and survival.
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PMID:New directions for emerging therapies in acute myeloid leukemia: the next chapter. 3312 75


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