American Society of Hematology

Figure 1.

$Figure 1. Families in this study and the selection process of patient data. Individuals who have been genotyped for the ERCC6L2 c.1457delT mutation are marked with an asterisk (*). Black dots (•) represent heterozygous carriers of the mutation. Probands in each family are marked with arrows. (A) Families (1-3) in the discovery set. Family 1: patient 1445 was age 38 years when referred to hematologist because of pancytopenia. His BM was dysplastic with strong erythroid predominance and an excess of myeloid blasts. Aiming at allogeneic hematopoietic stem cell transplantation (HSCT), his 36-year-old sister (patient 1458) was examined as a donor candidate. Tests revealed peripheral blood cytopenias. The following BM examination revealed MDS, which quickly progressed to AML M6. She died as a result of refractory leukemia. Patient 1445 underwent HSCT from a registry donor but relapsed quickly with a therapy-resistant AML M6 and died as a result of the disease. Family 2: the index patient (1450) age 18 years was diagnosed with BMF of unknown origin and referred to the hematology department in 2018. Her 2 paternal aunts (patients 1459 and 1439) had died as a result of AML M6. The twin sister (patient 1463) of the index’s father had mild thrombocytopenia and was diagnosed with BMF and 3 acquired TP53 mutations along with this study. Family 3: patient 1438 had spontaneously recovered from aplastic anemia in her childhood. At age 31 years, while pregnant, she was identified as having persistent thrombocytopenia. A next-generation sequencing myeloid gene panel on her peripheral blood sample detected a somatically mutated TP53 clone. BM samples showed severe BMF. (B) Analysis of the validation set. One (patient 1443) of 7 AML M6 patients was found homozygous for ERCC6L2 c.1457delT. Family 4: patient 1443 was age 65 years when diagnosed with AML M6. His sister had died as a result of severe aplastic anemia (or BMF) at a young age. (C) No ERCC6L2 c.1457delT homozygotes were found in the control set of 165 AML patients with other subtypes. Mut, mutated; tAML, therapy-related AML; wt, wild type.$

Families in this study and the selection process of patient data. Individuals who have been genotyped for the ERCC6L2 c.1457delT mutation are marked with an asterisk (*). Black dots (•) represent heterozygous carriers of the mutation. Probands in each family are marked with arrows. (A) Families (1-3) in the discovery set. Family 1: patient 1445 was age 38 years when referred to hematologist because of pancytopenia. His BM was dysplastic with strong erythroid predominance and an excess of myeloid blasts. Aiming at allogeneic hematopoietic stem cell transplantation (HSCT), his 36-year-old sister (patient 1458) was examined as a donor candidate. Tests revealed peripheral blood cytopenias. The following BM examination revealed MDS, which quickly progressed to AML M6. She died as a result of refractory leukemia. Patient 1445 underwent HSCT from a registry donor but relapsed quickly with a therapy-resistant AML M6 and died as a result of the disease. Family 2: the index patient (1450) age 18 years was diagnosed with BMF of unknown origin and referred to the hematology department in 2018. Her 2 paternal aunts (patients 1459 and 1439) had died as a result of AML M6. The twin sister (patient 1463) of the index’s father had mild thrombocytopenia and was diagnosed with BMF and 3 acquired TP53 mutations along with this study. Family 3: patient 1438 had spontaneously recovered from aplastic anemia in her childhood. At age 31 years, while pregnant, she was identified as having persistent thrombocytopenia. A next-generation sequencing myeloid gene panel on her peripheral blood sample detected a somatically mutated TP53 clone. BM samples showed severe BMF. (B) Analysis of the validation set. One (patient 1443) of 7 AML M6 patients was found homozygous for ERCC6L2 c.1457delT. Family 4: patient 1443 was age 65 years when diagnosed with AML M6. His sister had died as a result of severe aplastic anemia (or BMF) at a young age. (C) No ERCC6L2 c.1457delT homozygotes were found in the control set of 165 AML patients with other subtypes. Mut, mutated; tAML, therapy-related AML; wt, wild type.

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