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Determining the frequency of iron overload at diagnosis in de novo acute myeloid leukemia patients with multilineage dysplasia or myelodysplasia-related changes: a case control study

  • Boran YavuzEmail author
  • Seda Aydın
  • Süreyya Bozkurt
  • Ayşegül Üner
  • Yahya Büyükaşık
Original Article

Abstract

Acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC) is a new disease category, which was defined as a separate entity in the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. While pre-treatment iron overload in patients with myelodysplastic syndrome has been previously studied, its relationship with AML-MRC has not been studied. We aimed to investigate the relationship between serum iron tests compatible with iron overload and the diagnosis of multilineage dysplasia (MLD) and AML with myelodysplasia-related changes (AML-MRC) in AML patients diagnosed at Hacettepe University Adult Hospital between January 2002 and September 2017. Ninety-three patients who met the criteria were enrolled. Bone marrow aspirate of each patient was re-examined, and dysplasia was investigated; other data were examined from patient’s records. The iron overload status at diagnosis and transferrin saturation (TS) values were compared between the groups with and without MLD and those with and without AML-MRC. When iron overload was defined as TS ≥ 58% and ferritin ≥ 500 ng/mL, iron overload was observed in 10 (37%) patients with MLD and in 4 (13%) without MLD. The difference is almost statistically significant (p = 0.053). The mean TS value and frequency of iron overload were higher in AML-MRC patients than in non-AML-MRC patients (p < 0.05 for both). A mild positive significant correlation was observed between the dysplasia severity score and TS (r = 0.317, p = 0.032). In patients with AML-MLD and AML-MRC, iron overload occurred regardless of the transfusion status at the time of diagnosis. Morphologic severity of dysplasia may be correlated with higher TS values at the time of diagnosis.

Keywords

Acute myeloid leukemia AML with myelodysplasia-related changes Iron overload Multilineage dysplasia Transferrin saturation 

Notes

Funding

While there was not substantial funding needed for this research, it was done using the research infrastructure of Hacettepe University and Ankara University.

Compliance with ethical standards

This study was approved by the Ethics Committee for Non-Interventional Clinical Investigations of Hacettepe University on December 27, 2017 (decision number GO 17/794-28).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Swerdlow SCE, Lee Harris N et al (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edn. IARC Press, LyonGoogle Scholar
  2. 2.
    Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405.  https://doi.org/10.1182/blood-2016-03-643544 CrossRefGoogle Scholar
  3. 3.
    Brito-Babapulle F, Catovsky D, Galton DA (1987) Clinical and laboratory features of de novo acute myeloid leukaemia with trilineage myelodysplasia. Br J Haematol 66(4):445–450CrossRefGoogle Scholar
  4. 4.
    Cortelezzi A, Cattaneo C, Cristiani S, Duca L, Sarina B, Deliliers GL, Fiorelli G, Cappellini MD (2000) Non-transferrin-bound iron in myelodysplastic syndromes: a marker of ineffective erythropoiesis? Hematol J 1(3):153–158.  https://doi.org/10.1038/sj/thj/6200028 CrossRefGoogle Scholar
  5. 5.
    Cui R, Gale RP, Zhu G, Xu Z, Qin T, Zhang Y, Huang G, Li B, Fang L, Zhang H, Pan L, Hu N, Qu S, Xiao Z (2014) Serum iron metabolism and erythropoiesis in patients with myelodysplastic syndrome not receiving RBC transfusions. Leuk Res 38(5):545–550.  https://doi.org/10.1016/j.leukres.2014.01.016 CrossRefGoogle Scholar
  6. 6.
    Miesner M, Haferlach C, Bacher U, Weiss T, Macijewski K, Kohlmann A, Klein HU, Dugas M, Kern W, Schnittger S, Haferlach T (2010) Multilineage dysplasia (MLD) in acute myeloid leukemia (AML) correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: a comparison of 408 cases classified as “AML not otherwise specified” (AML-NOS) or “AML with myelodysplasia-related changes” (AML-MRC). Blood 116(15):2742–2751.  https://doi.org/10.1182/blood-2010-04-279794 CrossRefGoogle Scholar
  7. 7.
    Schildgen V, Wulfert M, Gattermann N (2011) Impaired mitochondrial gene transcription in myelodysplastic syndromes and acute myeloid leukemia with myelodysplasia-related changes. Exp Hematol 39(6):666–675 e661.  https://doi.org/10.1016/j.exphem.2011.03.007 CrossRefGoogle Scholar
  8. 8.
    Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Lowenberg B, Bloomfield CD (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–447.  https://doi.org/10.1182/blood-2016-08-733196 CrossRefGoogle Scholar
  9. 9.
    Elsayed ME, Sharif MU, Stack AG (2016) Transferrin saturation: a body iron biomarker. Adv Clin Chem 75:71–97.  https://doi.org/10.1016/bs.acc.2016.03.002 CrossRefGoogle Scholar
  10. 10.
    Lyle L, Hirose A (2018) Iron overload in myelodysplastic syndromes: pathophysiology, consequences, diagnosis, and treatment. J Adv Pract Oncol 9(4):392–405Google Scholar
  11. 11.
    Moukalled NM, El Rassi FA, Temraz SN, Taher AT (2018) Iron overload in patients with myelodysplastic syndromes: an updated overview. Cancer 124(20):3979–3989.  https://doi.org/10.1002/cncr.31550 CrossRefGoogle Scholar
  12. 12.
    Ballen KK, Gilliland DG, Kalish LA, Shulman LN (1994) Bone marrow dysplasia in patients with newly diagnosed acute myelogenous leukemia does not correlate with history of myelodysplasia or with remission rate and survival. Cancer 73(2):314–321CrossRefGoogle Scholar
  13. 13.
    Weinberg OK, Pozdnyakova O, Campigotto F, DeAngelo DJ, Stone RM, Neuberg D, Hasserjian RP (2015) Reproducibility and prognostic significance of morphologic dysplasia in de novo acute myeloid leukemia. Mod Pathol 28(7):965–976.  https://doi.org/10.1038/modpathol.2015.55 CrossRefGoogle Scholar
  14. 14.
    Devillier R, Gelsi-Boyer V, Brecqueville M, Carbuccia N, Murati A, Vey N, Birnbaum D, Mozziconacci MJ (2012) Acute myeloid leukemia with myelodysplasia-related changes are characterized by a specific molecular pattern with high frequency of ASXL1 mutations. Am J Hematol 87(7):659–662.  https://doi.org/10.1002/ajh.23211 CrossRefGoogle Scholar
  15. 15.
    Vardiman J, Reichard K (2015) Acute myeloid leukemia with myelodysplasia-related changes. Am J Clin Pathol 144(1):29–43.  https://doi.org/10.1309/AJCP58RSMFRHLHHH CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Internal Medicine, School of MedicineHacettepe UniversityAnkaraTurkey
  2. 2.Department of Internal Medicine, Section of Hematology, School of MedicineHacettepe UniversityAnkaraTurkey
  3. 3.Department of Medical Biology, School of Medicineİstinye UniversityIstanbulTurkey
  4. 4.Department of Pathology, School of MedicineHacettepe UniversityAnkaraTurkey

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