Growth factor independent 1b (Gfi1b) and a new splice variant of Gfi1b are highly expressed in patients with acute and chronic leukemia.
Gfi1b is a transcriptional repressor that is essential for erythroid cells and megakaryocytes, but is also expressed in hematopoietic stem cells and early myeloid progenitors. The chromosomal localization of the Gfi1b gene at 9q34 and its functional homology with the proto-oncogene Gfi1 were suggestive for a role of Gfi1b in malignant transformation and myeloid leukemia. We show here that the expression of Gfi1b is strongly elevated in CML and AML patients compared to normal healthy controls and that imatinib, a drug widely used to treat CML, further enhances Gfi1b expression in patients even after remission. Our data suggest that Gfi1b may be an important factor to establish or maintain myeloid leukemia and myeloproliferative diseases and that, high expression levels of Gfi1b might be associated with the emergence of Philadelphia chromosome negative myeloid malignancies after imatinib withdrawal or after the development of imatinib resistance.
Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Virchowstrasse 173, 45122, Essen, Germany.|Institut de recherches cliniques de Montreal, IRCM, 110 Avenue des Pins West, Montreal, QC, H2W 1R7, Canada.
Lothar
L
Vassen
Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Virchowstrasse 173, 45122, Essen, Germany.|Institut de recherches cliniques de Montreal, IRCM, 110 Avenue des Pins West, Montreal, QC, H2W 1R7, Canada.
Cyrus
C
Khandanpour
Department for Internal Medicine, Center for Cancer Research, Universitätsklinikum Essen, 45122, Essen, Germany.
Peter
P
Ebeling
Central Hematology Laboratory, Radboud University Nijmegen Medical Centre for Molecular Life Sciences (NCMLS), PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Bert A
BA
van der Reijden
Central Hematology Laboratory, Radboud University Nijmegen Medical Centre for Molecular Life Sciences (NCMLS), PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Joop H
JH
Jansen
Department of Internal Medicine and Hematology, Universitätsklinikum Essen, 45122, Essen, Germany.
Stefan
S
Mahlmann
Department of Internal Medicine and Hematology, Universitätsklinikum Essen, 45122, Essen, Germany.
Ulrich
U
Dührsen
Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Virchowstrasse 173, 45122, Essen, Germany. Tarik.Moroy@ircm.qc.ca.|Institut de recherches cliniques de Montreal, IRCM, 110 Avenue des Pins West, Montreal, QC, H2W 1R7, Canada. Tarik.Moroy@ircm.qc.ca.|Departement de Microbiologie et Immunologie, Université de Montréal, Montréal, Canada. Tarik.Moroy@ircm.qc.ca.
Tarik
T
Möröy
D000208:Acute Disease; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D019556:COS Cells; D002522:Chlorocebus aethiops; D002908:Chronic Disease; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
D000970:Antineoplastic Agents; D001549:Benzamides; C400551:GLI1 protein, human; C000715470:MAS1 protein, human; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines; D012333:RNA, Messenger; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases