Table 1.

Genes involved in predisposition to myelodysplastic syndrome

Cellular function, syndrome, geneInheritanceHematologic malignancyOther malignancyVariable associated phenotypes
DNA repair     
 Fanconi anemia     
  FANCA AR MDS, AML Squamous cell carcinoma: oral, gastrointestinal, genitourinary; FANCD1/BRCA2 subtype also presents with other solid tumors and ALL. Bone marrow failure, short stature, hyper/hypopigmentation, facial dysmorphologies, skeletal, digits, hypogonadism, cardiopulmonary, gastrointestinal, endocrinopathies, CNS 
  FANCB XLR 
  FANCC AR 
  FANCD1/BRCA2 AR 
  FANCD2 AR 
  FANCE AR 
  FANCF AR 
  FANCG AR 
  FANCI AR 
  FANCJ/BRIP1/BACH1 AR 
  FANCL AR 
  FANCM AR 
  FANCN/PALB2 AR 
  FANCO/RAD51C AR 
  FANCP/SLX4 AR 
  FANCQ/ERCC4 AR 
  FANCR/RAD51 AD 
  FANCS/BRCA1 AR 
  FANCT/UBE2T AR 
  FANCU/XRCC2 AR 
  FANCV/REV7 AR 
  FANCW/RFWD3 AR    
Transcription factor     
 Familial platelet disorder with propensity to myeloid malignancy     
  RUNX1 AD MDS, AML, T-ALL, hairy cell leukemia  Thrombocytopenia, platelet dysfunction 
 GATA2-spectrum disorders     
  GATA2 AD MDS, AML, CMML, JMML  Emberger syndrome, MonoMac syndrome, immunodeficiencies/immune dysregulation (monocytopenia, B-cell deficiencies, NK cell deficiencies), hearing loss, warts, atypical mycobacterial infections, lymphedema, monocytopenia, marrow failure 
 Thrombocytopenia 5     
  ETV6 AD ALL, MDS, AML, CMML, MM  Thrombocytopenia, platelet dysfunction 
Ribosomal abnormalities     
 Diamond Blackfan anemia     
  GATA1 AD MDS, AML Osteosarcoma, soft tissue sarcomas Bone marrow failure, short stature, radial ray abnormalities, cardiac, renal anomalies, facial dysmorphisms 
  RPL5 AD 
  RPL11 AD 
  RPL15 AD 
  RPL23 AD 
  RPL26 AD 
  RPL27 AD 
  RPL31 AD 
  RPL35a AD 
  RPL36 AD 
  RPS7 AD 
  RPS10 AD 
  RPS15 AD 
  RPS17 AD 
  RPS19 AD 
  RPS24 AD 
  RPS26 AD 
  RPS27 AD 
  RPS27A AD 
  RPS28 AD 
  RPS29 AD 
  TSR2 X-linked 
 Shwachman Diamond syndrome     
  SBDS AR MDS, AML  Bone marrow failure, short stature, exocrine pancreatic dysfunction, skeletal dysplasias, immunodeficiencies, neurocognitive, other congenital anomalies 
  DNAJC21 AR AML  
  EFL1 AR ?  
Telomere maintenance     
 DC/TBD     
  DKC1 XLR MDS, AML Oral and gastrointestinal squamous cell carcinoma Bone marrow failure, nail dystrophy, skin pigmentation abnormalities, oral leukoplakia, idiopathic pulmonary fibrosis, liver disease, short telomeres, immunodeficiencies, vascular anomalies, other congenital anomalies 
  TERC AD 
  TERT AD, AR 
  NOLA3/NOP10 AR 
  NOLA2/NHP2 AR 
  TINF2 AD 
  WRAP53/TCAB1 AR 
  CTC1 AR 
  RTEL1 AD, AR 
  ACD/ TPP1 AD, AR 
  PARN AD, AR 
  NAF1 AD 
  STN1 AD 
RAS pathway     
 Noonan syndrome     
  PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF, MAP2K1 AD JMML, MDS, AML, MPN Solid tumors Facial dysmorphism, short stature, cardiac, broad neck, thoracic, cryptorchidism, coagulopathy (Noonan) 
 Noonan-like    
  CBL AD JMML, MDS  
Other     
 Severe congenital neutropenia     
  ELANE AD MDS, AML (ALL?)  Osteopenia 
  HAX1 AR MDS, AML (ALL?)  Seizures, neurologic abnormalities 
  GFI1 AD MDS, AML  Lymphopenia 
  G6PC3 AR MDS, AML  Neutropenia, congenital heart malformations, prominent superficial veins, urogenital abnormalities, Dursun syndrome 
  JAGN1 AR AML  Skeletal and dental abnormalities 
 Thrombocytopenia 2     
  ANKRD26 AD MDS, AML, CLL, CMML  Thrombocytopenia, platelet dysfunction 
 X-linked neutropenia     
  WAS X-linked MDS, AML  Immunologic abnormalities, monocytopenia 
 MIRAGE syndrome, (myelodysplasia, infection, restriction of growth, adrenal insufficiency, genital phenotypes, and enteropathy)     
  SAMD9 AD MDS, AML  Cytopenias, immunologic abnormalities, short stature, adrenal hypoplasia, infections, gastrointestinal, genitourinary skeletal, CNS, monosomy 7 
 Ataxia-pancytopenia syndrome     
  SAMD9L AD MDS, AML  Bone marrow failure, ataxia, monosomy 7 
 Neurofibromatosis 1     
  NF1 AD JMML, MDS Optic gliomas, CNS tumors, malignant peripheral nerve sheath tumors, other solid tumors Café au lait spots, axillary freckling, Lisch nodules, neurofibromas 
 Bloom syndrome     
  BLM AR Lymphoma, ALL, MDS, AML  Short stature, sun-sensitive rash, pulmonary disease, immunodeficiency 
 Constitutional mismatch repair deficiency     
  MLH1 AR ALL, Lymphoma, MDS, AML Gastrointestinal (colon), ovarian, uterine, CNS, other  
  MSH2 AR 
  MSH6 AR 
  EPCAM AR 
  PMS2 AR 
 Li-Fraumeni     
  TP53 AD ALL, MDS, AML, lymphoma Breast, osteosarcoma, soft tissue sarcoma, CNS, adrenocortical carcinoma, other  
 Susceptibility to acute myeloid leukemia     
  DDX41 AD MDS, AML, CML, lymphoma  Malignancies present in older age (>50 y) 
 Familial myeloproliferative neoplasms     
  JAK2 haplotype 46/1 [GGCC], TERT rs2736100_c AD PV, ET, PMF   
  ATG2B, GSKIP AD PV, ET, PMF, CML, CMML, AML 
  RBBP6 AD PV, ET, PMF 
 Myeloid neoplasms associated with trisomy 8 mosaicism     
  Trisomy 8 Variable MDS, AML, CML   
 Congenital neutropenia or SDS-Like disorder     
  SRP54 AR ?  Bone marrow failure, short stature, exocrine pancreatic dysfunction, skeletal dysplasias, immunodeficiencies 
 Bone Marrow Failure Syndrome 1     
  SRP72 AD MDS  Bone marrow failure, sensorineural hearing loss 
Cellular function, syndrome, geneInheritanceHematologic malignancyOther malignancyVariable associated phenotypes
DNA repair     
 Fanconi anemia     
  FANCA AR MDS, AML Squamous cell carcinoma: oral, gastrointestinal, genitourinary; FANCD1/BRCA2 subtype also presents with other solid tumors and ALL. Bone marrow failure, short stature, hyper/hypopigmentation, facial dysmorphologies, skeletal, digits, hypogonadism, cardiopulmonary, gastrointestinal, endocrinopathies, CNS 
  FANCB XLR 
  FANCC AR 
  FANCD1/BRCA2 AR 
  FANCD2 AR 
  FANCE AR 
  FANCF AR 
  FANCG AR 
  FANCI AR 
  FANCJ/BRIP1/BACH1 AR 
  FANCL AR 
  FANCM AR 
  FANCN/PALB2 AR 
  FANCO/RAD51C AR 
  FANCP/SLX4 AR 
  FANCQ/ERCC4 AR 
  FANCR/RAD51 AD 
  FANCS/BRCA1 AR 
  FANCT/UBE2T AR 
  FANCU/XRCC2 AR 
  FANCV/REV7 AR 
  FANCW/RFWD3 AR    
Transcription factor     
 Familial platelet disorder with propensity to myeloid malignancy     
  RUNX1 AD MDS, AML, T-ALL, hairy cell leukemia  Thrombocytopenia, platelet dysfunction 
 GATA2-spectrum disorders     
  GATA2 AD MDS, AML, CMML, JMML  Emberger syndrome, MonoMac syndrome, immunodeficiencies/immune dysregulation (monocytopenia, B-cell deficiencies, NK cell deficiencies), hearing loss, warts, atypical mycobacterial infections, lymphedema, monocytopenia, marrow failure 
 Thrombocytopenia 5     
  ETV6 AD ALL, MDS, AML, CMML, MM  Thrombocytopenia, platelet dysfunction 
Ribosomal abnormalities     
 Diamond Blackfan anemia     
  GATA1 AD MDS, AML Osteosarcoma, soft tissue sarcomas Bone marrow failure, short stature, radial ray abnormalities, cardiac, renal anomalies, facial dysmorphisms 
  RPL5 AD 
  RPL11 AD 
  RPL15 AD 
  RPL23 AD 
  RPL26 AD 
  RPL27 AD 
  RPL31 AD 
  RPL35a AD 
  RPL36 AD 
  RPS7 AD 
  RPS10 AD 
  RPS15 AD 
  RPS17 AD 
  RPS19 AD 
  RPS24 AD 
  RPS26 AD 
  RPS27 AD 
  RPS27A AD 
  RPS28 AD 
  RPS29 AD 
  TSR2 X-linked 
 Shwachman Diamond syndrome     
  SBDS AR MDS, AML  Bone marrow failure, short stature, exocrine pancreatic dysfunction, skeletal dysplasias, immunodeficiencies, neurocognitive, other congenital anomalies 
  DNAJC21 AR AML  
  EFL1 AR ?  
Telomere maintenance     
 DC/TBD     
  DKC1 XLR MDS, AML Oral and gastrointestinal squamous cell carcinoma Bone marrow failure, nail dystrophy, skin pigmentation abnormalities, oral leukoplakia, idiopathic pulmonary fibrosis, liver disease, short telomeres, immunodeficiencies, vascular anomalies, other congenital anomalies 
  TERC AD 
  TERT AD, AR 
  NOLA3/NOP10 AR 
  NOLA2/NHP2 AR 
  TINF2 AD 
  WRAP53/TCAB1 AR 
  CTC1 AR 
  RTEL1 AD, AR 
  ACD/ TPP1 AD, AR 
  PARN AD, AR 
  NAF1 AD 
  STN1 AD 
RAS pathway     
 Noonan syndrome     
  PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF, MAP2K1 AD JMML, MDS, AML, MPN Solid tumors Facial dysmorphism, short stature, cardiac, broad neck, thoracic, cryptorchidism, coagulopathy (Noonan) 
 Noonan-like    
  CBL AD JMML, MDS  
Other     
 Severe congenital neutropenia     
  ELANE AD MDS, AML (ALL?)  Osteopenia 
  HAX1 AR MDS, AML (ALL?)  Seizures, neurologic abnormalities 
  GFI1 AD MDS, AML  Lymphopenia 
  G6PC3 AR MDS, AML  Neutropenia, congenital heart malformations, prominent superficial veins, urogenital abnormalities, Dursun syndrome 
  JAGN1 AR AML  Skeletal and dental abnormalities 
 Thrombocytopenia 2     
  ANKRD26 AD MDS, AML, CLL, CMML  Thrombocytopenia, platelet dysfunction 
 X-linked neutropenia     
  WAS X-linked MDS, AML  Immunologic abnormalities, monocytopenia 
 MIRAGE syndrome, (myelodysplasia, infection, restriction of growth, adrenal insufficiency, genital phenotypes, and enteropathy)     
  SAMD9 AD MDS, AML  Cytopenias, immunologic abnormalities, short stature, adrenal hypoplasia, infections, gastrointestinal, genitourinary skeletal, CNS, monosomy 7 
 Ataxia-pancytopenia syndrome     
  SAMD9L AD MDS, AML  Bone marrow failure, ataxia, monosomy 7 
 Neurofibromatosis 1     
  NF1 AD JMML, MDS Optic gliomas, CNS tumors, malignant peripheral nerve sheath tumors, other solid tumors Café au lait spots, axillary freckling, Lisch nodules, neurofibromas 
 Bloom syndrome     
  BLM AR Lymphoma, ALL, MDS, AML  Short stature, sun-sensitive rash, pulmonary disease, immunodeficiency 
 Constitutional mismatch repair deficiency     
  MLH1 AR ALL, Lymphoma, MDS, AML Gastrointestinal (colon), ovarian, uterine, CNS, other  
  MSH2 AR 
  MSH6 AR 
  EPCAM AR 
  PMS2 AR 
 Li-Fraumeni     
  TP53 AD ALL, MDS, AML, lymphoma Breast, osteosarcoma, soft tissue sarcoma, CNS, adrenocortical carcinoma, other  
 Susceptibility to acute myeloid leukemia     
  DDX41 AD MDS, AML, CML, lymphoma  Malignancies present in older age (>50 y) 
 Familial myeloproliferative neoplasms     
  JAK2 haplotype 46/1 [GGCC], TERT rs2736100_c AD PV, ET, PMF   
  ATG2B, GSKIP AD PV, ET, PMF, CML, CMML, AML 
  RBBP6 AD PV, ET, PMF 
 Myeloid neoplasms associated with trisomy 8 mosaicism     
  Trisomy 8 Variable MDS, AML, CML   
 Congenital neutropenia or SDS-Like disorder     
  SRP54 AR ?  Bone marrow failure, short stature, exocrine pancreatic dysfunction, skeletal dysplasias, immunodeficiencies 
 Bone Marrow Failure Syndrome 1     
  SRP72 AD MDS  Bone marrow failure, sensorineural hearing loss 

AD, autosomal dominant; AR, autosomal recessive; CMML, chronic myelomonocytic leukemia; ET, essential thrombocythemia; JMML, juvenile myelomonocytic leukemia; PMF, primary myelofibrosis; PV, polycythemia vera.

Because of space limitations, this table is not exhaustive and readers are referred to additional references cited in the text.

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