The T-lineage-affiliated CD2 gene lies within an open chromatin environment in acute promyelocytic leukemia cells.
The nature of hemopoietic progenitors subject to leukemic transformation in acute myeloid leukemia (AML) has not been clearly defined. To address this issue, we have used DNase I hypersensitivity assays to study the chromatin structure surrounding the T-lineage-affiliated CD2 gene in the acute promyelocytic subtype of AML (APL). Upstream and downstream flanking regions of CD2 were found to be hypersensitive to DNase I in primary APL blasts, with an identical pattern of hypersensitive sites to those detected in cells of T-lineage. All of the sites were confirmed to be inaccessible to DNase I in B-lineage leukemia cells. The demonstration of T-cell-associated chromatin features in primary APL blasts has implications for the origin of APL that may arise in more primitive progenitors than previously considered to be the case.
Division of Medical and Molecular Genetics, Guy's, King's and St. Thomas' School of Medicine, London SE1 9RT, UK. david.grimwade@kcl.ac.uk
David
D
Grimwade
Susan V
SV
Outram
Rajinder
R
Flora
Stuart J
SJ
Ings
Arnold R
AR
Pizzey
Ricardo
R
Morilla
Charles F
CF
Craddock
David C
DC
Linch
Ellen
E
Solomon
D018801:CD2 Antigens / Q000235:genetics*; D019070:Cell Lineage; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D003850:Deoxyribonuclease I / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D019169:Jurkat Cells; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*
D018801:CD2 Antigens; D002843:Chromatin; D003850:Deoxyribonuclease I