Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151825 (bone pain)
 3,118 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is the first report in Israel of the successful treatment of acute promyelocytic leukemia (APL; M3) with an active metabolite of vitamin A. In a 42-year-old woman with APL all-trans-retinoic acid (ATRA; tretinoin), 45 mg/m2/day was given per os for 90 days. APL is associated with a distinct cytogenetic abnormality: translocation of a portion of the long arm chromosome 17 onto the long arm chromosome 15t (15; 17) with a breakpoint on chromosome 17 in the region of the retinoic acid receptor-alpha (RAR-alpha), playing a crucial role in the leukemogenesis of APL. In man, the drug induces myeloid and mainly promyelocytic leukemic cells to differentiate, without the development of bone marrow hypoplasia. In our patient it caused complete remission and the disappearance of intravascular disseminated coagulation. The only side-effects were a transient macular rash, gastrointestinal symptoms and mild hypertriglyceridemia. Other principal adverse effects reported in the literature are relatively not very serious and consist of dryness of the skin, occasional headaches and intracranial hypertension, nasal congestion, lymphadenopathy, respiratory distress with infiltrates in the lung, bone pain and increased hepatic aminotransferase. A hyperleukocytosis syndrome seems to be more problematic. ATRA appears to be superior to conventional chemotherapeutic regimens. It is safe and highly effective in inducing clinical, morphologic and karyotypic remission with a marked decrease in the expression of the abnormal RAR-message in APL. There is a possible molecular link between the pathogenesis and treatment of this severe and often fatal coagulopathic disease. This therapy of course does not eradicate the leukemic clone, and consolidation chemotherapy or bone marrow transplantation is necessary.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Remission of acute promyelocytic leukemia after all-trans-retinoic acid]. 148 98

A case of acute promyelocytic leukemia (APL) with RUNX1T1 insertion to 7q is described and compared to reported cases of APL with negative retinoic acid receptor alpha (RARA) abnormality. In this report, we describe the case of a 2-year-old boy who presented with bone pain and was found to have pancytopenia. Bone marrow examination showed morphologic and immunophenotypic findings typical of APL, but conventional cytogenetics, fluorescence in situ hybridization (FISH), and real-time polymerase chain reaction (RT-PCR) showed no evidence of RARA rearrangements. The only cytogenetic abnormality found was a small insertion in 7q, and three copies of RUNX1T1. Gene sequencing results became available after initiating therapy but were not informative. We describe the rarity of such cases and discuss how the typical morphologic and immunophenotypic findings of APL, coupled with the definite absence of RARA rearrangement (by FISH and RT-PCR), present a diagnostic and classification dilemma, raising the possibility of an unknown alternative mechanism for the leukemogenesis and maturation arrest seen in other APL variants. The diagnostic challenges and urgent management issues this unusual case raises may justify including it, along with similar cases, in a separate subtype of acute myeloid leukemia (AML) in future classifications.
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PMID:Promyelocytic Leukemia with No Retinoic Acid Receptor Alpha Abnormality but with RUNX1T1 Insertion to Chromosome 7q: A Classification and Management Dilemma. 2635 94