title: BP1, a new homeobox gene, is frequently expressed in acute leukemias.
abstract: Aberrant expression of homeobox genes has been described in primary leukemia blasts. We recently cloned a new cDNA, BP1, which is a member of the homeobox gene family. BP1 expression was investigated in bone marrow samples from acute myeloid leukemia (AML), acute T cell lymphocytic leukemia (ALL) and pre-B cell ALL. Expression levels of two apparent isoforms of BP1, DLX7 and DLX4, were measured in the same samples. They are weakly if at all detectable in normal bone marrow, PHA-stimulated T cells or B cells. BP1 RNA was highly expressed in 63% of AML cases, including 81% of the pediatric and 47% of the adult cases, and in 32% of T-ALL cases, but was not found in any of the pre-B ALL cases. Coexpression of BP1, DLX7 and DLX4 occurred in a significant number of leukemias. Our data, including co-expression of BP1 with c-myb and GATA-1, markers of early progenitors, suggest that BP1 expression occurs in primitive cells in AML. Analysis of CD34+ and CD34- normal bone marrow cells revealed BP1 is expressed in CD34- cells and virtually extinguished in CD34+ cells. Ectopic expression of BP1 in the leukemia cell line K562 increased clonogenicity, consistent with a role for BP1 in leukemogenesis. The presence of BP1 RNA in leukemic blasts may therefore be a molecular marker for primitive cells and/or may indicate that BP1 is an important upstream factor in an oncogenic pathway.
authors.affiliation: Division of Human Genetics, University of Maryland School of Medicine, Baltimore, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Haga
authors.forename: S
authors.initials: S
authors.lastname: Fu
authors.forename: J E
authors.initials: JE
authors.lastname: Karp
authors.forename: D D
authors.initials: DD
authors.lastname: Ross
authors.forename: D M
authors.initials: DM
authors.lastname: Williams
authors.forename: W D
authors.initials: WD
authors.lastname: Hankins
authors.forename: F
authors.initials: F
authors.lastname: Behm
authors.forename: F W
authors.initials: FW
authors.lastname: Ruscetti
authors.forename: M
authors.initials: M
authors.lastname: Chang
authors.forename: B D
authors.initials: BD
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Becton
authors.forename: S C
authors.initials: SC
authors.lastname: Raimondi
authors.forename: P E
authors.initials: PE
authors.lastname: Berg
mesh_terms: D000208:Acute Disease; D000367:Age Factors; D017398:Alternative Splicing; D014408:Biomarkers, Tumor / Q000235:genetics; D001856:Bone Marrow Examination; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D015973:Gene Expression Regulation, Leukemic; D005801:Genes, Homeobox; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D020014:K562 Cells / Q000166:cytology; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D015513:Oncogene Proteins; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014410:Tumor Stem Cell Assay
chemical_list: D014408:Biomarkers, Tumor; C105304:DLX4 protein, human; D018076:DNA, Complementary; D004273:DNA, Neoplasm; C104149:Dlx4 protein, mouse; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors