Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myosin light chain genes of human hematopoietic cells have not been fully characterized. We previously reported the cloning of the full-length cDNAs of 20 kDa regulatory myosin light chain (MLC-2), named as MLC-2A, from Meg-01, a human megakaryoblastic leukemia cell line (J. Smooth Muscle Res. 37: 25-38, 2001). We now cloned another MLC-2 isoforms from human platelets and U937, a human monocytic leukemia cell line, named as MLC-2B and MLC-2C, respectively. Both MLC-2A and MLC-2B consisted of three exons, which were situated on gene loci 18p1.3. Analysis of the gene structure indicated that MLC-2A and MLC-2B utilized different exons. MLC-2C also consisted of three exons, which was situated on gene loci 20p12. Amino acid sequence of MLC-2C was, of interest, apparently almost the same as that of MLC-2 from chicken gizzard smooth muscle LC20-A (one amino acid's difference) and human vascular smooth muscle LC-20 (two amino acids' difference). All three protein kinase C phosphorylation residues (Ser-1, Ser-2, Thr-9) and both myosin light chain kinase phosporylation residues (Thr-18, Ser-19) are conserved in these three isoforms. The MLC-2A and MLC-2B mRNA were expressed constitutively in all of the human hematopoietic cell lines examined and their expression levels were almost the same. On the other hand, MLC-2C mRNA was expressed in untreated monocytic cell lines (U937 and A-THP-1) and HL-60 differentiated into monocyte/macrophage cell lineage by TPA treatment. These results indicate that smooth muscle type isoform, MLC-2C is the inducible isoform, and might play a crucial role in monocyte/macrophage cell lineage.
 ...
PMID:Smooth muscle type isoform of 20 kDa myosin light chain is expressed in monocyte/macrophage cell lineage. 1848 May 96

Acute myeloid leukemia (AML) is an aggressive hematological malignancy. Nearly 50% of the patients who receive the most intensive treatment develop chemoresistant leukemia relapse. Although the leukemogenic events leading to relapse seem to differ between patients (i.e., regrowth from a clone detected at first diagnosis, progression from the original leukemic or preleukemic stem cells), a common characteristic of relapsed AML is increased chemoresistance. The aim of the present study was to investigate at the proteomic level whether leukemic cells from relapsed patients present overlapping molecular mechanisms that contribute to this chemoresistance. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to compare the proteomic and phosphoproteomic profiles of AML cells derived from seven patients at the time of first diagnosis and at first relapse. At the time of first relapse, AML cells were characterized by increased levels of proteins important for various mitochondrial functions, such as mitochondrial ribosomal subunit proteins (MRPL21, MRPS37) and proteins for RNA processing (DHX37, RNA helicase; RPP40, ribonuclease P component), DNA repair (ERCC3, DNA repair factor IIH helicase; GTF2F1, general transcription factor), and cyclin-dependent kinase (CDK) activity. The levels of several cytoskeletal proteins (MYH14/MYL6/MYL12A, myosin chains; VCL, vinculin) as well as of proteins involved in vesicular trafficking/secretion and cell adhesion (ITGAX, integrin alpha-X; CD36, platelet glycoprotein 4; SLC2A3, solute carrier family 2) were decreased in relapsed cells. Our study introduces new targetable proteins that might direct therapeutic strategies to decrease chemoresistance in relapsed AML.
 ...
PMID:The Progression of Acute Myeloid Leukemia from First Diagnosis to Chemoresistant Relapse: A Comparison of Proteomic and Phosphoproteomic Profiles. 3251 67