Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0038002 (
splenomegaly
)
9,873
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Aberrant signaling triggered by oncogenic or hyperactive RAS proteins contributes to the malignant phenotypes in a significant percentage of myeloid malignancies. Of these, juvenile myelomonocytic leukemia (JMML), an aggressive
childhood cancer
, is largely driven by mutations in
RAS
genes and those that encode regulators of these proteins. The
Mx1-cre kras
+/G12D
mouse model mirrors several key features of this disease and has been used extensively to determine the utility and mechanism of small molecule therapeutics in the context of RAS-driven myeloproliferative disorders. Treatment of disease-bearing KRAS
G12D
mice with rigosertib (RGS), a small molecule RAS mimetic that is in phase II and III clinical trials for MDS and AML, decreased the severity of leukocytosis and
splenomegaly
and extended their survival. RGS also increased the frequency of HSCs and rebalanced the ratios of myeloid progenitors. Further analysis of KRAS
G12D
HSPCs
in vitro
revealed that RGS suppressed hyperproliferation in response to GM-CSF and inhibited the phosphorylation of key RAS effectors. Together, these data suggest that RGS might be of clinical benefit in RAS-driven myeloid disorders.
...
PMID:Rigosertib ameliorates the effects of oncogenic KRAS signaling in a murine model of myeloproliferative neoplasia. 3095 75
Acute leukemia is the most common type of cancer in pediatric patients. This type of cancer accounts for a third of all
childhood cancer
cases. More than half of pediatric acute leukemia patients show signs and symptoms such as hepatomegaly,
splenomegaly
, pallor, fever and bruising at the time of diagnosis. In early stages of acute lymphoblastic leukemia (ALL), nephromegaly and other renal manifestations such as high blood pressure (HBP) and renal failure are uncommon, although renal infiltration and nephromegaly are common in advanced-stage pediatric patients. This is a retrospective case review with a critical appraisal of the existing evidence from the literature. We present a clinical case of a child with HBP associated with bilateral nephromegaly which resolved after chemotherapy treatment. This patient presented with HBP that required pharmacological treatment, likely owing to nephromegaly. All HBP secondary causes were rejected. Nephromegaly was resolved after chemotherapy treatment, and antihypertensive medication was discontinued. Nephromegaly and HBP are rare manifestations of ALL debut in pediatrics. The present case report illustrates this unusual combination and Suggests clinicians to consider malignancy as its causal factor, especially if the symptoms are accompanied by other suggestive extrarenal manifestations.
...
PMID:Renal involvement at diagnosis of pediatric acute lymphoblastic leukemia. 3230 71
