Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CBL and CBL-B ubiquitin ligases play key roles in hematopoietic stem cell homeostasis and their aberrations are linked to leukemogenesis. Mutations of CBL, often genetically-inherited, are particularly common in Juvenile Myelomonocytic Leukemia (JMML), a disease that manifests early in children. JMML is fatal unless corrected by bone marrow transplant, which is effective in only half of the recipients, stressing the need for animal models that recapitulate the key clinical features of this disease. However, mouse models established so far only develop hematological malignancy in adult animals. Here, using VAV1-Cre-induced conditional CBL/CBL-B double knockout (DKO) in mice, we established an animal model that exhibits a neonatal myeloproliferative disease (MPD). VAV1-Cre induced DKO mice developed a strong hematological phenotype at postnatal day 10, including severe leukocytosis and hepatomegaly, bone marrow cell hypersensitivity to cytokines including GM-CSF, and rapidly-progressive disease and invariable lethality. Interestingly, leukemic stem cells were most highly enriched in neonatal liver rather than bone marrow, which, along with the spleen and thymus, were hypo-cellular. Nonetheless, transplantation assays showed that both DKO bone marrow and liver cells can initiate leukemic disease in the recipient mice with seeding of both spleen and bone marrow. Together, our results support the usefulness of the new hematopoietic-specific CBL/CBL-B double KO animal model to study JMML-related pathogenesis and to further understand the function of CBL family proteins in regulating fetal and neonatal hematopoiesis. To our knowledge, this is the first mouse model that exhibits neonatal MPD in infancy, by day 10 of postnatal life.
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PMID:VAV1-Cre mediated hematopoietic deletion of CBL and CBL-B leads to JMML-like aggressive early-neonatal myeloproliferative disease. 2744 97

Chronic lymphocytic leukemia (CLL) is a disorder entailing the slow proliferation of B-cell lymphocytes in the bone marrow and blood. In 2015, it is estimated that 14,620 patients will be diagnosed with CLL, and approximately 4,650 patients will die due to disease progression. CLL typically presents in patients about 71 years of age. Initially, the patients exhibit leukocytosis; however, as the disease progresses, they experience splenomegaly, lymphadenopathy, hepatomegaly, anemia, and infections. Although about 84% of CLL patients will survive for five years or more, CLL cases that report MYC (8q24) translocations with IGH, IGK, IGL, and TCR genes have poor prognoses and low survival rates. Recent studies have shown data supporting both a positive correlation and no correlation between disease progression and MYC expression. Nonetheless, other studies have revealed new information on multiple MYC-dependent pathways responsible for leukemogenesis and tumorigenesis. Herein, we summarize the current molecular nd cytogenetic findings in MYC-associated CLL, with focus on the underlying MYC-dependent mechanisms of leukemogenesis and MYC-associated CLL progression and treatment regimen.
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PMID:C-MYC Involvement in Chronic Lymphocytic Leukemia (CLL): A Molecular and Cytogenetic Update. 2783 39