Myelodysplastic Syndrome: Causes

Pathogenesis (disease development)

Myelodysplastic syndrome disorders are clonal disorders of hematopoiesis (blood formation), meaning that there are qualitative and quantitative changes in hematopoiesis as well as peripheral cytopenia (decreased number of cells in the blood).

The defect is in the pluripotent stem cell (stem cells that can differentiate into any cell type of an organism) itself. Consequently, hematological changes may affect one, several or all blood cell lines. When the blood cells originate from a pathological (diseased) clone, they are limited in their ability to function and have a shortened survival time in the bone marrow as well as in the peripheral blood. The loss of the ability of the to differentiate results in increasing cytopenia (decrease in the number of cells in the blood), which may ultimately progress to acute myeloid leukemia (AML).

In primary myelodysplastic syndrome, clonal chromosomal aberrations (chromosomal abnormalities) can be detected in approximately 50% of patients. The most common is deletion (loss of a DNA segment) of chromosomes 5 (-5/5q), 7 (-7/7q), 20 (20q-) or the Y chromosome, as well as trisomy 8 (+8). In secondary myelodysplastic syndromes, the rate of aberrations is higher.

According to the cause, myelodysplastic syndrome can be classified into the following forms:

• Primary myelodysplastic syndrome (>90%).
  • Without identifiable cause
• Secondary myelodysplastic syndrome (<10%).
  • Therapy-associated myelodysplastic syndrome.
    • After previous cytostatic therapy (synonym: chemotherapy) – alkylants, topoisomerase II inhibitors, cisplatin, fludarabine, azathioprine.
    • After radiatio (radiotherapy)
    • After combined radiochemotherapy (RCTX; v. a. Alkylanzien in combination with radiation therapy).
    • After radioiodine therapy
  • Triggered by long-term exposure (10-20 years) to toxic (poisonous) substances such as benzenes and also certain solvents – particularly affected are gas station workers, painters and varnishers, as well as airport workers (kerosene).

Etiology (causes) of secondary myelodysplastic syndrome

Radiotherapy

• Combined radiochemotherapy (RCTX; mainly alkylating agents in combination with radiation therapy).
• Radioiodine therapy
• Radiotherapy (Radiatio)

Chemotherapies

• Combined radiochemotherapy (RCTX; v. Alkylanzien in combination with radiation therapy).
• Prior cytostatic therapy (synonym: chemotherapy).
  • Alkylants, topoisomerase II inhibitors, cisplatin, fludarabine, azathioprine.
  • Solid tumors (highest risk: bone cancer (SIR 39.0; 95% confidence interval 21.4-65.5), soft tissue cancer (SIR 10.4; 6.4-15.9), and testicular cancer (SIR, 12.3; 7.6-18.8); tumors in peritoneum, lungs (small cell carcinoma), ovary, fallopian tubes, or central nervous system: SIR 5 to 9 times; other cancers: SIR 1.5 to 4 times).

Environmental pollution – intoxications (poisonings).

• Long-term exposure (10-20 years) to toxic (poisonous) substances such as benzenes and also certain solvents – particularly affected are gas station workers, painters and painters, and also airport workers (kerosene).
• Lead
• Insecticides