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

A decade ago, gene expression profiling (GEP) was successfully introduced in haematological research. Considering the heterogeneity of haematological malignancies, the growing arsenal of compounds, allowing targeted therapy, e.g. in myelodysplastic syndromes (MDS) or chronic myeloid leukaemia (CML), and the more differentiated indication to allogeneic stem cell transplantation, routine diagnostic procedures would highly benefit from an introduction of this novel methodology: by now, the majority of genetically defined leukaemia subtypes has been accurately reproduced on the basis of distinct gene expression patterns by various independent research groups. Moreover, classification of histomorphologically overlapping lymphoma subentities (e.g. Burkitt lymphoma and diffuse large B-cell lymphoma, DLBCL), was considerably improved by GEP. Beyond that, differential gene expression has provided the basis for assays being able to predict prognosis of individual patients as well as the response to specific treatment approaches, e.g. to lenalidomide in MDS. In a high proportion of Philadelphia positive acute lymphoblastic leukaemia (ALL) patients, prognostically adverse deletions of the IKZF1 gene coding for a specific transcription factor were identified with GEP analysis, which revealed new insights in the clinical variability of this disorder. Given these advantages of GEP, the introduction of this methodology in current diagnostic algorithms of haematological malignancies should further be validated in clinical studies.
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PMID:Gene expression profiling for diagnosis and therapy in acute leukaemia and other haematologic malignancies. 2057 Apr 45

EphA3 is an Ephrin receptor tyrosine kinase that is overexpressed in most hematologic malignancies. We performed a first-in-human multicenter phase I study of the anti-EphA3 monoclonal antibody KB004 in refractory hematologic malignancies in order to determine safety and tolerability, along with the secondary objectives of pharmacokinetics (PK) and pharmacodynamics (PD) assessments, as well as preliminary assessment of efficacy. Patients were enrolled on a dose escalation phase (DEP) initially, followed by a cohort expansion phase (CEP). KB004 was administered by intravenous infusion on days 1, 8, and 15 of each 21-day cycle in escalating doses. A total of 50 patients (AML 39, MDS/MPN 3, MDS 4, DLBCL 1, MF 3) received KB004 in the DEP; an additional 14 patients were treated on the CEP (AML 8, MDS 6). The most common toxicities were transient grade 1 and grade 2 infusion reactions (IRs) in 79% of patients. IRs were dose limiting above 250mg. Sustained exposure exceeding the predicted effective concentration (1ug/mL) and covering the 7-day interval between doses was achieved above 190mg. Responses were observed in patients with AML, MF, MDS/MPN and MDS. In this study, KB004 was well tolerated and clinically active when given as a weekly infusion.
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PMID:KB004, a first in class monoclonal antibody targeting the receptor tyrosine kinase EphA3, in patients with advanced hematologic malignancies: Results from a phase 1 study. 2857 98