Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 78-year-old male, who had CKD and chronic heart failure, was referred to our hospital for evaluation of leukocytosis. His bone marrow contained 12% blast cells and chromosome analysis showed the Ph chromosome as well as other changes. The patient was diagnosed with the accelerated-phase CML because FISH and RT-PCR disclosed BCR/ABL fusion signals and minor BCR/ABL, respectively. Imatinib was administered, but the CML was resistant to this treatment. We gave him nilotinib employing a reduced and intermittent administration protocol because of the progression of anemia and heart failure. The patient achieved PCyR in 8 months, but, 12 months later, his WBC count increased and 83% of the cells were blasts. Because the probable diagnosis was the blast crisis of CML, we switched from nilotinib to dasatinib. However, leukocytosis worsened and he died of pneumonia. It was later revealed that he had a normal karyotype and both FISH and RT-PCR analysis of BCR/ABL were negative. His final diagnosis was Ph negative AML developing from Ph positive CML in PCyR. Since there were no dysplastic changes indicative of MDS, it was assumed that the AML was not secondary leukemia caused by the tyrosine kinase inhibitor but, rather, de novo AML.
...
PMID:[Development of Ph negative acute myeloid leukemia in a patient with minor-BCR/ABL positive chronic myeloid leukemia achieving a partial cytogenetic response during tyrosine kinase inhibitor treatment]. 2625 79

Chronic myelomonocytic leukemia (CML) is a myeloid tumor characterized by MDS (myelodysplastic syndrome) and MPN (myeloproliferative neoplasms). Allogeneic hematopoietic stem cell transplantation, chemotherapy, interferon, and targeted therapy are the main treatment methods for CML. Tyrosine kinase inhibitors (TKIs) are also a treatment option, and patients are currently recommended to take these drugs throughout their lives to prevent CML recurrence. Therefore, there is a need to investigate and identify other potential chemotherapy drugs. Currently, research on CML treatment with a single drug has shown little progress. Fingolimod (FTY720), an FDA-approved drug used to treat relapsing multiple sclerosis, has also shown great potential in the treatment of lymphocytic leukemia. In our study, we find that FTY720 and curcumol have a significant inhibitory effect on K562 cells, K562/ADR cells, and CD34+ cells from CML patients. RNAseq data analysis shows that regulation of apoptosis and differentiation pathways are key pathways in this process. Besides, BCR/ABL-Jak2/STAT3 signaling, PI3K/Akt-Jnk signaling, and activation of BH3-only genes are involved in CML inhibition. In a K562 xenograft mouse model, therapy with curcumol and FTY720 led to significant inhibition of tumor growth and induction of apoptosis. To summarize, curcumol and FTY720 synergistically inhibit proliferation involved in differentiation and induce apoptosis in CML cells. Therefore, synergistic treatment with two drugs could be the next choice of treatment for CML.
 ...
PMID:Curcumol and FTY720 synergistically induce apoptosis and differentiation in chronic myelomonocytic leukemia via multiple signaling pathways. 3327 66


<< Previous 1 2 3