Table 2.

Genes associated primarily with risk for hematopoietic cancer

Gene(s)	Condition	Hematopoietic cancer(s)	Prevalence of hematopoietic cancers36,40	Laboratory features	Other features
ANKRD26	ANKRD26-related thrombocytopenia	AML, CML	Unknown	Thrombocytopenia	None
BTK	X-linked agammaglobulinemia	ALL, lymphoma	Unknown	B-cell deficiency, agammaglobulinemia	Recurrent infection
CBL	CBL syndrome	JMML	<1%		Neurological features
					Noonan syndrome phenotype
CEBPA	Familial AML	AML/MDS	Unknown		None
DDX41	Familial AML	AML/MDS	Unknown		None
ELANE, HAX1, G6PC3	Congenital neutropenias	AML/MDS	∼10%	Neutropenia	Cardiovascular and/or urogenital abnormalities (G6PC3)
					Pulmonary hypertension (G6PC3)
ETV6	Familial leukemia	ALL, less commonly MDS/AML, CMML, T/myeloid mixed phenotype leukemia	Unknown	Thrombocytopenia, red cell macrocytosis	None
FAS, FASLG, CASP10	Autoimmune lymphoproliferative syndrome	Lymphoma	8-12%	Lymphoproliferation	Autoimmune disease
				Autoimmune cytopenias
GATA2	Familial AML and Emberger syndromes	AML/MDS	50% or greater	Neutropenia; dendritic cell, monocyte, B-cell and NK cell depletion	Primary lymphedema
					Warts
					Deafness
KLHDC8B	Lymphoma predisposition	Hodgkin lymphoma	Unknown		None
MPL	Congenital amegakaryocytic thrombocytopenia	AML/MDS	2%	Thrombocytopenia	Possibly CNS abnormalities
				Megakaryocytopenia
				Bone marrow failure
Multiple	Severe combined immunodeficiency	B-cell lymphoma	Unknown	Immunodeficiency	Failure to thrive
					Recurrent infection
					Autoimmunity
					Short stature
NPAT	Lymphoma predisposition	Nodular lymphocyte predominant, Hodgkin lymphoma	Unknown		None
PAX5	Leukemia predisposition	ALL	Unknown	Chromosome 9p loss in leukemia cells	None
RBM8A	Thrombocytopenia absent radius syndrome	ALL, AML/MDS	1%	Thrombocytopenia	Absent radii
					Other skeletal anomalies
					Heart defects, genitourinary defects
					Cow’s milk intolerance
RUNX1	Familial platelet disorder with associated myeloid malignancy	AML/MDS, CMML	∼35%	Thrombocytopenia	None
SBDS	Shwachman-Diamond syndrome	ALL, AML/MDS	5-36%	Bone marrow failure	Pancreatic insufficiency
					Short stature
					Skeletal abnormalities
SH2B3	Leukemia predisposition	ALL	Unknown		Growth retardation, developmental delays
					Autoimmune disorders
SH2D1A	X-linked lymphoproliferative disease	NHL (B-cell)	∼24%	HLH-associated EBV infection	Aplastic anemia Vasculitis
				Dysgamma globulinemia
SRP72	SRP72-associated familial aplasia and myelodysplasia	AML	Unknown	Aplastic anemia	Deafness
Trisomy 21	Down syndrome	ALL, AML, TMD	10% (TMD)		Multiple congenital anomalies
			∼2-3% (ALL, AML)		Dysmorphic features
					Intellectual disability
Unknown	Familial monosomy 7 syndrome	AML/MDS, ALL	Unknown	Acquired monosomy 7	None
				Bone marrow failure
				Red cell macrocytosis
				Increased HbF
WAS	WAS-related disorders (including Wiskott-Aldrich syndrome)	ALL, lymphoma	∼2% (ALL)	Thrombocytopenia neutropenia	Eczema
			∼13% (lymphoma)	Immunodeficiency	Autoimmune disorders

CML, chronic myeloid leukemia; CNS, central nervous system; HbF, hemoglobin F; HLH, hemophagocytic lymphohistiocytosis.