title: ID2 and ID3 protein expression mirrors granulopoietic maturation and discriminates between acute leukemia subtypes.
abstract: The inhibitors of DNA binding (ID) inhibit basic helix-loop-helix transcription factors and thereby guide cellular differentiation and proliferation. To elucidate the involvement of IDs in hematopoiesis and acute leukemias (AL), we analyzed ID2 and ID3 expression in hematopoiesis and leukemic blasts in bone marrow biopsies (BMB). BMB of healthy stem cell donors (n = 19) and BMB of patients with acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MD; n = 19), de novo AML (n = 20), B-acute lymphoblastic leukemia (B-ALL) (n = 23), T-ALL (n = 19), were immunohistochemically stained for ID2 and ID3 expression. The expression patterns were evaluated and quantified for each hematopoietic lineage and each leukemia subtype. In normal BMB, immature granulopoiesis showed weak ID2 and strong ID3 expression, which was lost during maturation (p < 0.001). Erythropoiesis remained negative for ID2/3 (p < 0.001). ID2/3 expression differed between immature granulopoiesis and leukemic blasts (p < 0.001). Moreover, differential ID2/3 expression was seen between AL subgroups: AML, especially AML-MD, had more ID2- (p < 0.001) and ID3-positive (p < 0.001) blasts than ALL. We show a comprehensive in situ picture of ID2/3 expression in hematopoiesis and AL. Morphologically, ID2/3 proteins seem to be involved in the granulopoietic maturation. Importantly, the distinct ID2/3 expression patterns in AL indicate a specific deregulation of ID2/3 in the various types of AL and may support subtyping of AL.
authors.affiliation: Department of Pathology, University Medical Center, Breisacher Str. 115a, 79106, Freiburg, Germany.
authors.forename: Annette M
authors.initials: AM
authors.lastname: May
authors.forename: Anna-Verena
authors.initials: AV
authors.lastname: Frey
authors.forename: Lioudmila
authors.initials: L
authors.lastname: Bogatyreva
authors.forename: Marco
authors.initials: M
authors.lastname: Benkisser-Petersen
authors.forename: Dieter
authors.initials: D
authors.lastname: Hauschke
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.forename: Ralph
authors.initials: R
authors.lastname: Wäsch
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.forename: Jens
authors.initials: J
authors.lastname: Hasskarl
authors.forename: Silke
authors.initials: S
authors.lastname: Lassmann
mesh_terms: D001706:Biopsy; D001854:Bone Marrow Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D005260:Female; D006098:Granulocytes / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000032:analysis / Q000096:biosynthesis*; D051796:Inhibitor of Differentiation Proteins / Q000032:analysis* / Q000096:biosynthesis*; D015470:Leukemia, Myeloid, Acute / Q000145:classification* / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis*; D012189:Retrospective Studies
chemical_list: C497450:ID2 protein, human; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; C075640:ID3 protein, human