BackgroundMyelodysplastic syndromes and acute myeloid leukemia usually occur sporadically in older adults. More recently cases of familial acute myeloid leukemia and/or myelodysplastic syndrome have been reported.Case presentationCurrently we report a father and son who both developed myelodysplastic syndrome that progressed to acute myeloid leukemia. Both patients were found to have the identical mutation of ASXL1 on nextgen sequencing of both hematologic and nonhematologic tissues.ConclusionsThese cases support the diagnosis of a germline mutation of ASXL1.

Hematologic malignancies have generally been considered to be sporadic diseases. More recently several germ line mutations that lead to hereditary hematologic malignancies have been discovered, even in adults. We sought to evaluate the frequency of a family history of hematologic or other malignancy in pts admitted to the hospital for treatment of a hematologic malignancy. We also studied exposure history including use of cigarettes. All pts signed informed consent. Pts were entered prospectively and interviewed with a standard questionnaire. 702 pts (median age 61.9: range 16.3-91.3 years) were enrolled. Diagnoses were AML: 396 pts, aplastic anemia: 5 pts, ALL: 96 pts, CLL: 24 pts, CML 42 pts, CMML 10 pts, MDS 30 pts, MM 19 pts, MPD 10 pts, and NHL 70 pts. 473 pts (67.4%) had a family member with cancer. There was a total of 1037 cancers in these family members. The median number of family members with cancer was 1 (range 0-10). The frequency of each type of family member cancer is displayed in the table. 19.7% of pts had a family member with leukemia or other hematologic malignancy (leukemia: 12.0%, other hematologic: 7.7%). Compared to pts with a hematologic malignancy other than AML, pts with AML were more likely to have a family member with any type of cancer (72.4% vs 60.7%, p=0.001). Pts with AML were also more likely to have a family member with a history of any type of hematologic malignancy (22.4% vs 16.0%, p=0.03), but not specifically a history of leukemia (13.4% vs 10.1%, p=0.11). Compared to pts with hematologic malignancies other than AML, pts with AML were also more likely to have a family member with prostate cancer (16.2% vs 9.5%, p=0.01), or breast cancer (29.5% vs 21.9%, p=0.02). 51.4% of pts had a history of smoking (either current or prior). Pts with AML were more likely to be current or former smokers compared to pts with other hematologic malignancies (55.8% vs 45.8%, p=0.008). These data support the role of genetics and exposure in adults with AML. Figure 1 Figure 1. Disclosures Seiter: Delta FLY: Research Funding; Novartis: Honoraria; Rafael: Research Funding; Sun Pharma: Research Funding; Jazz: Honoraria, Research Funding; Glycomimetics: Research Funding; Incyte: Honoraria; Forma: Research Funding; Celgene (BMS): Honoraria, Research Funding. Liu: Beigene: Honoraria, Speakers Bureau; Pfizer: Research Funding; Astellas: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Speakers Bureau; Incyte: Honoraria; Celgene: Research Funding.