Page 46 - 2020_08-Haematologica-web

A. Veninga et al.
Table 1. Relevant genes in clonal hematopoiesis with effects on platelet traits and disease.
Gene Gene Protein Overall role in Germline/ name (OMIM) function hematopoiesis somatic
Inherited disease classification (OMIM, PMID)
Dyschromatosis universalis hereditaria 3 (615402); Microphthalmia (614497); Pseudohyperkalemia familial 2 (609153); Blood group Langereis system (111600)
Congenital heart defect skeletal malformations syndrome (617602)
Bohring-Opitz syndrome (605039)
Undefined
Cardiofaciocutaneous syndrome
(115150); LEOPARD syndrome 3 (613707); Noonan syndrome 7 (613706)
Tatton-Brown- Rahman syndrome (615879)
Thrombocytopenia 5 (616216)
Fanconi
anemia complementation group A (227650)
Fanconi
anemia complementation group C (227645)
Somatic Mutation Mutation Thrombosis Bleeding Predisposition Ref.
phenotype (OMIM, PMID)
Undefined
Leukemia Philadelphia chromosome- positive resistant to imatinib (608232)
Myelodysplastic syndrome somatic (614286)
Acute
lymphocytic leukemia Philadelphia chromosome positive somatic (613065); Chronic myeloid leukemia Philadelphia chromosome positive somatic (608232)
effect on protein
Loss-of- function
Gain-of- function
Loss-of- function
effect on risk platelet traits
risk to malignancy
platelet traits
ABCB6 605452 Mitochondrial Mitochondiral
G,S
G,S
G,S
S
G,S
G,S
G,S
G,S
G,S
Count ↑, Yes size ↑,
No Undefined 11
No ALL, CML 18
No Aplastic 13 anemia,
AML, CMML, MDS, MPN
No ALL, CML 18
n.d. HCL, solid 20 cancers
transporter
stability
function ↑ (m)
ABL1 189980 Signaling Proliferation regulator and survival
of HSC
ASXL1 612990 Transcription Tumor regulator suppression; maintenance
of normal hematopoiesis
BCR 151410 Signaling Development regulator and survival
of HSC
BRAF 164757 Signaling Controlling protein development
kinase and proliferation of HSC
DNMT3A602769 Epigenetic Tumor regulator suppression
ETV6 600618 Transcription Development repressor and survival
of HSC; when fused either proto-oncogene or tumor suppressor
Count ↑ n.d. Count↑ Yes
Gain-of- function
(h, m)
Count ↑ n.d. Count ↑/= n.d.
Count ↑ Yes Count ↓, No
Count ↓ No (h, m)
Count ↓ No
Adenocarcinoma of lung somatic (211980); Colorectal and other cancers somatic
Acute myeloid leukemia somatic (601626)
Acute myeloid leukemia somatic (601262)
Undefined
Undefined
Gain-of- function
Loss-of- function
Loss-of- function
Loss-of- function
Loss-of- function
No AML, CMML, MDS, MPN (including
ET, PV)
26,28
size=, function ↓
Yes ALL (pre-B), 49 AML, MDS
Yes AML, MDS, 50 solid cancers
Yes AML, MDS, 50 solid cancers
FANCA 607139 DNA repair protein
FANCC 613899 DNA repair protein
Chromosomal stability regulating differentiation of HSC
Protection against cytotoxicity
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haematologica | 2020; 105(8)