WF Pink Group Research Proposal

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Pink Group

Project Overview

The subject of our research will be prohibiting leukemia characteristics through protein engineering. We would like to build on the work done by the Mark Offman group by considering additional mutations to the L-asparaginase enzyme.

Possible Areas to Mutate

  1. Mutations in the L-ASN enzyme that will allow it to evade leukemia cell digestion.
  2. Mutations in the L-ASN enzyme that will increase its ability to digest asparagine.

Background Information

  • Leukemia cells are unable to synthesize their own asparagine. L-asparaginase (L-ASN) degrades asparagine, making it unavailable to the leukimia cells. However, the cells posses mechanisms that digest L-ASN and therefore limit the drugs ability to starve the cells.
  • The Offman group predicted that N24T and N24A mutations would contribute to higher L-ASN activity .
  • Leukemia lymphoblasts have been observed to cleave L-ASN at N24.

Useful Articles

Rational engineering of L-asparaginase reveals importance of dual activity for cancer cell toxicity

  • Marc N. Offman,Marcin Krol, Naina Patel, Shekhar Krishnan, JiZhong Liu, Vaskar Saha, and Paul A. Bates

L-Asparagine depletion levels and L-asparaginase activity in plasma of children with acute lymphoblastic leukemia under asparaginase treatment

  • Masahito Tsurusawa, Motoaki Chin, Asayuki Iwai, Keiko Nomura, Hideaki Maeba, Takashi Taga,Takeshi Higa, Tomoko Kuno, Toshinori Hori, Akiko Muto, Miyo Yamagata

L-Asparaginase Treatment in Acute Lymphoblastic Leukemia

  • Rob Pieters, Stephen P. Hunger, Joachim Boos, Carmelo Rizzari, Lewis Silverman, Andre Baruchel, Nicola Goekbuget, Martin Schrappe, Ching-Hon Pui

Research Problem

Goals

Project Details and Methods

Outcome

Predicted Results