Stage- and lineage-specific expression of the HOXA10 homeobox gene in normal and leukemic hematopoietic cells.
There is growing evidence that the HOX homeobox-containing transcription factors are differentially expressed during hematopoiesis. We have previously demonstrated that the HOXA10 gene is expressed in unfractionated normal marrow and in immortalized leukemic cell lines with myelomonocytic features, but not in cell lines with lymphoid or erythroid features. To gain insights into the patterns of activation of this gene during hematopoietic differentiation, we have examined HOXA10 expression in CD34+ and CD34- subfractions of normal marrow and normal peripheral blood, as well as samples from patients with a variety of acute and chronic leukemias. HOXA10 is strongly expressed in CD34+ normal marrow cells, markedly downregulated in CD34- marrow cells, and inactive in mature neutrophils, monocytes, and lymphocytes. HOXA10 is expressed in all types of acute myelogenous leukemia (AML) with the notable exception of acute promyelocytic leukemia (AML-M3). HOXA10 message is observed in chronic myelogenous leukemia (CML) but appears to be reduced in accelerated phase and blast crisis, particularly lymphoid blast crisis. With rare exception, HOXA10 expression is not observed in samples of acute or chronic lymphoid leukemias. Normal marrow and patient samples appear to contain a single transcript which encodes a full-length homeobox-containing protein, while immortalized cell lines contain an additional alternatively spliced transcript. These studies indicate that HOXA10 expression is restricted to early stages of myeloid differentiation.
Lawrence
H J
HJ
Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Sauvageau
G
G
Ahmadi
N
N
Lopez
A R
AR
LeBeau
M M
MM
Link
M
M
Humphries
K
K
Largman
C
C
D001483:Base Sequence; D015139:Blotting, Southern; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D017931:DNA Primers; D018076:DNA, Complementary; D004273:DNA, Neoplasm / Q000032:analysis; D015870:Gene Expression; D005801:Genes, Homeobox; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism; D012016:Reference Values; D014158:Transcription, Genetic
D017931:DNA Primers; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; D004247:DNA