Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MLL aberrations are found in approximately 10% of acute leukemias. More than 80 different MLL fusion genes have been cytogenetically described but a significant number of MLL fusion partners remain unidentified on the molecular level. We describe here the case of a patient who developed secondary acute myeloid leukemia five years after the patient had received adjuvant radiochemotherapy because of breast cancer. This therapy comprised 4 cycles epirubicin/cyclophosphamide, a mitoxantrone-based high-dose chemotherapy with autologous stem cell transplantation and a subsequent radiation. Cytogenetic bone marrow analysis revealed a translocation t(11;14)(q23;q32), with a MLL split signal in FISH analysis. By applying a long-distance inverse PCR method the KIAA0284 gene was identified as translocation partner. Both breakpoints, on chromosomes 11 and 14, were characterized. The breakpoint in the KIAA0284 gene was located 5' of the putative start codon and an in-frame MLL-KIAA0284 transcript was detectable by RT-PCR. The KIAA0284 gene has hitherto not been implicated in hematologic diseases and has never been reported as a translocation partner. Its physiological function is unknown. The expression of KIAA0284 in various tissues and hematologic diseases was investigated by real time quantitative PCR and turned out to be very low in all lymphatic and myeloid diseases investigated.
Blood Cells Mol Dis
PMID:A MLL-KIAA0284 fusion gene in a patient with secondary acute myeloid leukemia and t(11;14)(q23;q32). 1864 63

Chromosomal rearrangements involving the MLL gene have been associated with many different types of hematological malignancies. Fluorescent in situ hybridization with a panel of probes coupled with long distance inverse-PCR was used to identify chromosomal rearrangements involving the MLL gene. Between 1995 and 2010, 27 patients with an acute leukemia were found to have a fusion gene involving MLL. All seven ALL patients with B cell acute lymphoblastic leukemia were characterized by the MLL/AFF1 fusion gene resulting from a translocation (5 patients) or an insertion (2 patients). In the 19 AML patients with acute myeloblastic leukemia, 31.6% of all characterized MLL fusion genes were MLL/MLLT3, 21.1% MLL/ELL, 10.5% MLL/MLLT6 and 10.5% MLL/EPS15. Two patients had rare or undescribed fusion genes, MLL/KIAA0284 and MLL/FLNA. Seven patients (26%) had a complex chromosomal rearrangement (three-way translocations, insertions, deletions) involving the MLL gene. Splicing fusion genes were found in three patients, leading to a MLL/EPS15 fusion in two and a MLL/ELL fusion in a third patient. This study showed that fusion involving the MLL gene can be generated through various chromosomal rearrangements such as translocations, insertions and deletions, some being complex or cryptic. A systematic approach should be used in all cases of acute leukemia starting with FISH analyses using a commercially available MLL split signal probe. Then, the analysis has to be completed, if necessary, by further molecular cytogenetic and genomic PCR methods.
Mol Oncol 2011 Dec
PMID:Identification of MLL partner genes in 27 patients with acute leukemia from a single cytogenetic laboratory. 2190 57

Microtubule dynamics are essential throughout mitosis to ensure correct chromosome segregation. Microtubule depolymerization is controlled in part by microtubule depolymerases, including the kinesin-13 family of proteins. In humans, there are three closely related kinesin-13 isoforms (Kif2a, Kif2b, and Kif2c/MCAK), which are highly conserved in their primary sequences but display distinct localization and nonoverlapping functions. Here we demonstrate that the N-terminus is a primary determinant of kinesin-13 localization. However, we also find that differences in the C-terminus alter the properties of kinesin-13, in part by facilitating unique protein-protein interactions. We identify the spindle-localized proteins Cep170 and Cep170R (KIAA0284) as specifically associating with Kif2b. Cep170 binds to microtubules in vitro and provides Kif2b with a second microtubule-binding site to target it to the spindle. Thus the intrinsic properties of kinesin-13s and extrinsic factors such as their associated proteins result in the diversity and specificity within the kinesin-13 depolymerase family.
Mol Biol Cell 2012 Dec
PMID:The microtubule-binding protein Cep170 promotes the targeting of the kinesin-13 depolymerase Kif2b to the mitotic spindle. 2308 11