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GATA-1 and GATA-2 gene expression is related to the severity of dysplasia in myelodysplastic syndrome

Leukemia volume 16, pages 1563–1565 (2002)Cite this article

Dysplasia of erythroid, granulocytic and megakaryocytic lineages is the diagnostic hallmark of myelodysplastic syndrome (MDS). The usual result is one or more peripheral blood cytopenias and an increased risk of leukemic transformation. Transcription factors play a key role in controlling the cellular proliferation and differentiation of hematopoietic stem cells.1,2 GATA-1 and GATA-2 are zinc-finger transcription factors that play an important role in gene regulation during development and differentiation of hematopoietic cells. Previous studies using GATA-1 and GATA-2 knock-out mice showed that GATA-2 gene inactivation caused partial deficiency in the production of hematopoietic lineages through its action in early progenitor or stem cell proliferation,2 while GATA-1 was important for erythroid differentiation of hematopoietic progenitor cells.3 The expression of GATA family genes and its implication in primary MDS has never been reported. Since inappropriate hematopoietic differentiation results in varying degree of myelodysplasia, which is the hallmark of MDS, we hypothesized that mRNA expression patterns of GATA-1 and GATA-2 are associated with MDS, and possibly with the severity of these diseases.

In this study, bone marrow (BM) specimens were obtained from 45 adult patients with primary MDS, including 24 patients with refractory anemia with excess of blasts or refractory anemia with excess of blasts in transformation (RAEB/RAEBT) and 21 patients with refractory anemia or refractory anemia with ring sideroblasts (RA/RARS). Peripheral blood (PB) samples from three normal individuals and BM specimens from eight patients with non-hematological diseases were used as controls. Two independent hematologists examined the BM aspirate specimens and trephine biopsy sections. Morphological features that were used to indicate dyserythropoiesis, dysgranulopoiesis and dysmegakaryopoiesis were based on the FAB group4 (Table 1). A scoring system based on features listed in Table 1 was developed to split the MDS patients into two groups morphologically according to the severity of myelodysplasia: severe or minimal dysplasia. The presence of less than one-third of the features was considered to be minimal dysplasia. This scoring system has been shown to correlate well with the degree of peripheral cytopenias in MDS; in addition, patients with severe dysplasia are more likely to be transfusion dependent (unpublished observations).

Table 1 Major features of dysplasia in myelodysplastic syndrome
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Acknowledgements

We are grateful to Mr Chua Kien Hui from the Bio-Diagnostic SDN BHD for his excellent technical assistance. This work was supported by a grant from the Intensification of Research In Priority Areas (IRPA- 06–02–02–0112) from the Ministry of Science and Technology, Malaysia.

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  1. Clinical Haematology and Stem Cell Transplantation Services, MAKNA-HUKM Cancer Institute, Hospital Universiti Kebangsaan Malaysia (HUKM), Kuala Lumpur, Malaysia

    S-A-W Fadilah, S-K Cheong & M Rozie-Hanisa

  2. Department of Medicine, Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur, Malaysia

    S-A-W Fadilah & H Roslan

  3. Department of Medicine, Universiti Malaya (UM), Kuala Lumpur, Malaysia

    G-K Yen

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Fadilah, SAW., Cheong, SK., Roslan, H. et al. GATA-1 and GATA-2 gene expression is related to the severity of dysplasia in myelodysplastic syndrome. Leukemia 16, 1563–1565 (2002). https://doi.org/10.1038/sj.leu.2402517

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