Related Experiment Video
Updated: May 26, 2026
Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
Published on: October 3, 2018
Familial aggregation of acute myeloid leukemia and myelodysplastic syndromes
Lynn R Goldin1, Sigurdur Y Kristinsson, Xueying Sharon Liang
1Genetic Epidemiology Branch, DCEG, NCI, 6120 Executive Blvd, Room 7124, MSC 7236, Bethesda, MD 20892-7236, USA. goldinl@mail.nih.gov
Purpose:
Apart from rare pedigrees with multiple cases of acute myeloid leukemia (AML), there is limited data on familial aggregation of AML and myelodysplastic syndromes (MDSs) in the population.
Patients And Methods:
Swedish population-based registry data were used to evaluate risk of AML, MDS, and other malignancies among 24,573 first-degree relatives of 6,962 patients with AML and 1,388 patients with MDS compared with 106,224 first-degree relatives of matched controls. We used a marginal survival model to calculate familial aggregation.
Results:
AML and/or MDS did not aggregate significantly in relatives of patients with AML. There was a modest risk ratio (RR, 1.3; 95% CI, 0.9 to 1.8) in myeloproliferative/myeloid malignancies combined. The risks for any hematologic or any solid tumor were modestly but significantly increased. Relatives of patients with MDS did not show an increased risk for any hematologic tumors. In contrast, we found a significantly increased risk (RR, 6.5; 95% CI, 1.1 to 38.0) of AML/MDS and of all myeloid malignancies combined (RR, 3.1; 95% CI, 1.0 to 9.8) among relatives of patients diagnosed at younger than age 21 years.
Conclusion:
We did not find evidence for familial aggregation of the severe end of the spectrum of myeloid malignancies (AML and MDS). The risks of myeloproliferative neoplasms were modestly increased with trends toward significance, suggesting a possible role of inheritance. In contrast, although limited in sample size, relatives of young patients with AML were at increased risk of AML/MDS, suggesting that germline genes may play a stronger role in these patients. The increased risk of all hematologic malignancies and of solid tumors among relatives of patients with AML suggests that genes for malignancy in general and/or other environmental factors may be shared.
Insights
Familial aggregation of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) was not significant overall. However, relatives of young AML patients showed increased AML/MDS risk, suggesting a potential genetic link.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Limited data exists on familial aggregation of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
- Understanding familial risk is crucial for identifying potential genetic predispositions.
Purpose of the Study:
- To investigate the familial aggregation of AML and MDS in the Swedish population.
- To assess the risk of AML, MDS, and other malignancies among first-degree relatives of patients diagnosed with AML or MDS.
Main Methods:
- Utilized Swedish population-based registry data for 6,962 AML and 1,388 MDS patients.
- Compared first-degree relatives of patients with matched controls using a marginal survival model.
Main Results:
- No significant familial aggregation of AML or MDS was observed in relatives of AML patients.
- A modest increased risk (RR 1.3) for combined myeloproliferative/myeloid malignancies was noted.
- Relatives of patients diagnosed with AML before age 21 showed a significantly increased risk (RR 6.5) of AML/MDS.
Conclusions:
- No strong evidence for familial aggregation of severe myeloid malignancies (AML/MDS).
- A possible role for inheritance in myeloproliferative neoplasms is suggested.
- Germline genes may play a significant role in AML/MDS for young-onset cases, warranting further investigation.
Related Concept Videos
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
03:03Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:15Differentiation of Common Myeloid Progenitor Cells