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Molecular analysis of genes expressed during megakaryocytic differentiation of the human myelogenous leukemic cell line K562

Morrow, Dwight Magnus
http://rave.ohiolink.edu/etdc/view?acc_num=case1060095314

Abstract Details

1992, Doctor of Philosophy, Case Western Reserve University, Pathology.
The work in this dissertation focuses on the genetic changes that take place as the human myelogenous leukemic cell line K562, following chemical induction, differentiates along the megakaryocytic lineage. The major objectives of the work were to develop methods to study those genetic changes and to use those methods to identify genes whose expression changes after K562 cells are induced to differentiate. The first method developed and employed for these studies was a modified differential screening protocol designed for the efficient identification of genes expressed in one cell state, but not in another. The second method developed represents a technological breakthrough for the identification and isolation of genes which play obligatory roles in cellular processes by the use of antisense RNA expression libraries to generate random sets of cellular mutants. Using my modified differential screening protocol to study megakaryocytic differentiation of K562 cells three genes whose expression level increases as differentiation proceeds were identified. The first gene identified was erythrocyte potentiating activity (EPA) also known as tissue inhibitor of metalloproteinase (TIMP). I show that EPA/TIMP i s highly expressed during megakaryocytic differentiation and present evidence that EPA/TIMP might not be a growth or differentiation factor as has been described. The second gene identified was cathepsin L, a proteinase, not previously known to be expressed by K562 cells. The third gene was placental protein 14 (PP14), an immunoregulatory protein described previously to be expressed only by tissues of the reproductive tract. Using supernatants from K562 cells containing PP14 a potent inhibition of mixed lymphocyte cultures (MLC) was observed. This immunosuppressive activity was specifically removed when anti-PP14 antibodies were added to the MLCs. I also identified a constitutively expressed, novel cDNA from K562 cells containing an Alu repetitive sequence highly represented in genes from cells with hematopoietic origin, particular erythrocytes and megakaryocytes. I provide evidence that Alu sequences play an important and perhaps critical role in the differentiation of K562 cells. It is my hope that these findings will aid our understanding of hematopoietic differentiation
Mark Tykocinski (Advisor)
206 p.
Biology, Molecular
Megakaryocytic differentiation; Myelogenous leukemic cell line K562

Recommended Citations

Citations

  • Morrow, D. M. (1992). Molecular analysis of genes expressed during megakaryocytic differentiation of the human myelogenous leukemic cell line K562 [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1060095314

    APA Style (7th edition)

  • Morrow, Dwight. Molecular analysis of genes expressed during megakaryocytic differentiation of the human myelogenous leukemic cell line K562. 1992. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1060095314.

    MLA Style (8th edition)

  • Morrow, Dwight. "Molecular analysis of genes expressed during megakaryocytic differentiation of the human myelogenous leukemic cell line K562." Doctoral dissertation, Case Western Reserve University, 1992. http://rave.ohiolink.edu/etdc/view?acc_num=case1060095314

    Chicago Manual of Style (17th edition)

case1060095314
467
© 1992, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.