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A team of researchers lead by Shweta Tyagi at the Centre for DNA Fingerprinting and Diagnostics, Hyderabad have come up with new insights into how mixed lineage leukemia (MLL) protein is closely associated with leukemia (blood cancer) in children and adults.
The team found the protein plays a crucial role in cell division by regulating chromosome segregation. Their work highlights that the absence of MLL itself gives rise to genomic instability and makes the cell prone to cancer. This study comes at a time when lot of effort is being put to find drug targets for leukemia.
This study provides insights into this novel function of MLL and Tyagi is optimistic that future work from her group would help in understanding how MLL regulates chromosome division and will provide a better drug target for blood cancer then being tested now.
Chromosomal translocations in the MLL gene occur frequently in acute myeloid and lymphoid leukemia. Such translocations give rise to new chimeric fusion proteins. Most researchers focus on how these fusion proteins may be causing cancer. Meanwhile, little effort is made to discover the essential cellular functions of MLL.
Tyagi’s group has been looking into find out how MLL regulates cell cycle, a process intimately linked with cancer. While undergoing cell division, all chromosomes align themselves in a straight line so that they can be divided equally into two daughter cells. To segregate, the chromosomes attach to spindle microtubules, which acts like ropes to pull the chromosomes to each end.
They observe that when they knock down MLL by RNAi, chromosomes keep trying to align but do not succeed. A process, which takes less than 40 minutes in a normal cell, goes on for several hours in the absence of MLL. As a result, both daughter cells do not receive equal number of chromosomes and such cells are highly likely to become cancerous.
Their findings show that MLL acts by recruiting key kinesin ‘motor’ protein Kif2A to mitotic spindles. Kif2A is responsible for organising the spindles and in the absence of MLL, it is unable to reach the spindles on its own. Kif2A is known to be associated with several kinds of cancers too.
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