Table 1 Characteristics of pre-BCR and... | American Society of Hematology

Table 1

Characteristics of pre-BCR⁺ and pre-BCR⁻ ALL subsets

Gene	Function	Type of defect	Functional outcome	Phenotype in disease model	Frequency in human ALL (%)			Reference
Gene	Function	Type of defect	Functional outcome	Phenotype in disease model	Total	Pre-BCR⁺	Pre-BCR⁻	Reference
CRLF2	Cytokine receptor	Overexpression	Cytokine receptor signaling ↑	Propensity to ALL	12*	0	15	9-11
CRLF2	Cytokine receptor	Rearrangement	Cytokine receptor signaling ↑	Propensity to ALL	12*	0	15	9-11
FLT3	Cytokine receptor	Point mutation	Cytokine receptor signaling ↑	Propensity to leukemia	2.5	0	3	9-11
IL7R	Cytokine receptor	Point mutation	Cytokine receptor signaling ↑	Propensity to ALL	2	0	2	9-11
PDGFRB	Cytokine receptor	Rearrangement	Cytokine receptor signaling ↑	Propensity to leukemia	1	0	1	9-11
EPOR	Cytokine receptor	Rearrangement	Cytokine receptor signaling ↑		<1	0	<1	9-11
JAK1, JAK2, JAK3	Tyrosine kinase	Point mutation	Cytokine receptor signaling ↑	Propensity to ALL	7*	0	9	9-11
JAK1, JAK2, JAK3	Tyrosine kinase	Rearrangement	Cytokine receptor signaling ↑	Propensity to ALL	7*	0	9	9-11
ABL1	Tyrosine kinase	BCR-ABL1	Cytokine receptor signaling ↑	ALL	3*-27†	0	4-35	9-11
ABL1	Tyrosine kinase	NUP214, ETV6, RCSD1	Cytokine receptor signaling ↑	Propensity to leukemia	1	0	2	9-11
SH2B3	Linker	Deletion	Cytokine receptor signaling ↑	Pro–B-cell block	2	0	2	9-11
IGHM	Ig heavy chain	Nonproductive V(D)J	No functional pre-BCR	B-cell autoimmunity	83	0	>80	54, 66
VPREB1	Surrogate light chain	Focal deletion	No functional pre-BCR	Pro–B-cell block	15	0	20	56
CD79A	(Pre-) BCR signaling chain	Transcriptional silencing	No functional pre-BCR	Pro–B-cell block	80	0	>80	54, 55
CD79B	(Pre-) BCR signaling chain	Transcriptional silencing	No functional pre-BCR	Pro–B-cell block	80	0	>80	54, 55
SYK	(Pre-) BCR tyrosine kinase	Aberrant splicing, mutation	Pre-BCR signaling ↓	Pro–B-cell block	<10	0	<10	54
BLNK	(Pre-) BCR linker	Aberrant splicing	Pre–B-cell differentiation ↓	Pre–B-cell block	40	0	∼50	53, 57
BLNK	(Pre-) BCR linker	Focal deletion	Cytokine receptor signaling ↑	Propensity to ALL	2	0	2	64
BTK	(Pre-) BCR tyrosine kinase	Aberrant splicing	Pre–B-cell differentiation ↓	Pre–B-cell block	30	0	∼25	58-60
BTK	(Pre-) BCR tyrosine kinase	Aberrant splicing	Pre–B-cell differentiation ↓	Propensity to ALL	30	0	∼25	58-60
PAX5	Transcription factor	Deletion, point mutation	Cytokine receptor signaling ↑	Propensity to ALL	∼25	10	∼25	64
BACH2	Transcription factor	Deletion 6q15	Pre-BCR signaling ↓	Propensity to ALL	20	0	∼25	34
IKZF1	Transcription factor	Deletion, point mutation	Pre-BCR signaling ↓	Propensity to ALL	20-84‡	0	∼25	64, 65
IKZF3	Transcription factor	Deletion	Pre-BCR signaling ↓	Propensity to ALL	2	0	2	64, 65
EBF1	Transcription factor	Deletion, point mutation	Pre-BCR signaling ↓	Propensity to ALL	6	0	8	64, 65
PBX1	Transcription factor	TCF3-PBX1 rearrangement	Pre-BCR signaling ↑	Propensity to ALL	3*-5†	40	0	66, 68
PBX1	Transcription factor	1q23 duplication	Pre-BCR signaling ↑	Propensity to ALL	1	5	0	66
PRDM1	Transcription factor	Deletion 6q21	Pre-BCR signaling ↑	Plasma cell defect	1	5	0	66

Gene	Function	Type of defect	Functional outcome	Phenotype in disease model	Frequency in human ALL (%)			Reference
Gene	Function	Type of defect	Functional outcome	Phenotype in disease model	Total	Pre-BCR⁺	Pre-BCR⁻	Reference
CRLF2	Cytokine receptor	Overexpression	Cytokine receptor signaling ↑	Propensity to ALL	12*	0	15	9-11
CRLF2	Cytokine receptor	Rearrangement	Cytokine receptor signaling ↑	Propensity to ALL	12*	0	15	9-11
FLT3	Cytokine receptor	Point mutation	Cytokine receptor signaling ↑	Propensity to leukemia	2.5	0	3	9-11
IL7R	Cytokine receptor	Point mutation	Cytokine receptor signaling ↑	Propensity to ALL	2	0	2	9-11
PDGFRB	Cytokine receptor	Rearrangement	Cytokine receptor signaling ↑	Propensity to leukemia	1	0	1	9-11
EPOR	Cytokine receptor	Rearrangement	Cytokine receptor signaling ↑		<1	0	<1	9-11
JAK1, JAK2, JAK3	Tyrosine kinase	Point mutation	Cytokine receptor signaling ↑	Propensity to ALL	7*	0	9	9-11
JAK1, JAK2, JAK3	Tyrosine kinase	Rearrangement	Cytokine receptor signaling ↑	Propensity to ALL	7*	0	9	9-11
ABL1	Tyrosine kinase	BCR-ABL1	Cytokine receptor signaling ↑	ALL	3*-27†	0	4-35	9-11
ABL1	Tyrosine kinase	NUP214, ETV6, RCSD1	Cytokine receptor signaling ↑	Propensity to leukemia	1	0	2	9-11
SH2B3	Linker	Deletion	Cytokine receptor signaling ↑	Pro–B-cell block	2	0	2	9-11
IGHM	Ig heavy chain	Nonproductive V(D)J	No functional pre-BCR	B-cell autoimmunity	83	0	>80	54, 66
VPREB1	Surrogate light chain	Focal deletion	No functional pre-BCR	Pro–B-cell block	15	0	20	56
CD79A	(Pre-) BCR signaling chain	Transcriptional silencing	No functional pre-BCR	Pro–B-cell block	80	0	>80	54, 55
CD79B	(Pre-) BCR signaling chain	Transcriptional silencing	No functional pre-BCR	Pro–B-cell block	80	0	>80	54, 55
SYK	(Pre-) BCR tyrosine kinase	Aberrant splicing, mutation	Pre-BCR signaling ↓	Pro–B-cell block	<10	0	<10	54
BLNK	(Pre-) BCR linker	Aberrant splicing	Pre–B-cell differentiation ↓	Pre–B-cell block	40	0	∼50	53, 57
BLNK	(Pre-) BCR linker	Focal deletion	Cytokine receptor signaling ↑	Propensity to ALL	2	0	2	64
BTK	(Pre-) BCR tyrosine kinase	Aberrant splicing	Pre–B-cell differentiation ↓	Pre–B-cell block	30	0	∼25	58-60
BTK	(Pre-) BCR tyrosine kinase	Aberrant splicing	Pre–B-cell differentiation ↓	Propensity to ALL	30	0	∼25	58-60
PAX5	Transcription factor	Deletion, point mutation	Cytokine receptor signaling ↑	Propensity to ALL	∼25	10	∼25	64
BACH2	Transcription factor	Deletion 6q15	Pre-BCR signaling ↓	Propensity to ALL	20	0	∼25	34
IKZF1	Transcription factor	Deletion, point mutation	Pre-BCR signaling ↓	Propensity to ALL	20-84‡	0	∼25	64, 65
IKZF3	Transcription factor	Deletion	Pre-BCR signaling ↓	Propensity to ALL	2	0	2	64, 65
EBF1	Transcription factor	Deletion, point mutation	Pre-BCR signaling ↓	Propensity to ALL	6	0	8	64, 65
PBX1	Transcription factor	TCF3-PBX1 rearrangement	Pre-BCR signaling ↑	Propensity to ALL	3*-5†	40	0	66, 68
PBX1	Transcription factor	1q23 duplication	Pre-BCR signaling ↑	Propensity to ALL	1	5	0	66
PRDM1	Transcription factor	Deletion 6q21	Pre-BCR signaling ↑	Plasma cell defect	1	5	0	66

Signaling	Function	Abnormality	Functional outcome	Phenotype in disease model	Frequency in human ALL (%)			Reference
Signaling	Function	Abnormality	Functional outcome	Phenotype in disease model	Total	Pre-BCR⁺	Pre-BCR⁻	Reference
STAT5	Transcription factor	Hyperphosphorylation	Cytokine receptor signaling ↑	Pro–B-cell survival ↓	∼40	0	>50	9-11, 66
BCL6	Transcription factor	Overexpression	Pre-BCR signaling ↑	Pre–B-cell survival ↓	13.5	>95	0	31-33, 66

Signaling	Function	Abnormality	Functional outcome	Phenotype in disease model	Frequency in human ALL (%)			Reference
Signaling	Function	Abnormality	Functional outcome	Phenotype in disease model	Total	Pre-BCR⁺	Pre-BCR⁻	Reference
STAT5	Transcription factor	Hyperphosphorylation	Cytokine receptor signaling ↑	Pro–B-cell survival ↓	∼40	0	>50	9-11, 66
BCL6	Transcription factor	Overexpression	Pre-BCR signaling ↑	Pre–B-cell survival ↓	13.5	>95	0	31-33, 66

Pediatric ALL.

†

Adult ALL.

‡

Ph⁺ ALL (BCR-ABL1).

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