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ID2 and ID3 protein expression mirrors granulopoietic maturation and discriminates between acute leukemia subtypes

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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.

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Acknowledgments

The authors thank Mrs. Katja Thurig for excellent technical assistance. ML, JH, and SL received funding for this study by the Deutsche-Jose-Carreras-Leukaemie-Stiftung (Grant No. DJCLS R 09/26).

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Authors and Affiliations

  1. Department of Pathology, University Medical Center, Breisacher Str. 115a, 79106, Freiburg, Germany

    Annette M. May, Anna-Verena Frey, Martin Werner & Silke Lassmann

  2. Institute of Medical Biometry and Medical Informatics, University Medical Center, Freiburg, Germany

    Lioudmila Bogatyreva & Dieter Hauschke

  3. Department of Hematology and Oncology, Comprehensive Cancer Center Freiburg (CCCF), University Medical Center, Freiburg, Germany

    Marco Benkisser-Petersen, Michael Lübbert, Ralph Wäsch & Jens Hasskarl

  4. Faculty of Biology, BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany

    Marco Benkisser-Petersen

  5. BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany

    Silke Lassmann

  6. Comprehensive Cancer Center Freiburg (CCCF), University Medical Center, Freiburg, Germany

    Michael Lübbert, Ralph Wäsch, Martin Werner & Silke Lassmann

  7. German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany

    Martin Werner & Silke Lassmann

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  1. Annette M. May
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Correspondence to Silke Lassmann.

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May, A.M., Frey, AV., Bogatyreva, L. et al. ID2 and ID3 protein expression mirrors granulopoietic maturation and discriminates between acute leukemia subtypes. Histochem Cell Biol 141, 431–440 (2014). https://doi.org/10.1007/s00418-013-1169-7

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