意义不明的克隆性细胞减少症
Clonal cytopenia of undetermined significance ，CCUS
夏成青
更新时间：2022-10-16 21:11:18
概述：
诊断要点：
2. 骨髓细胞学检查可能存在细胞异型，但不满足骨髓增生异常肿瘤（MDS）的诊断标准。
3. 骨髓活检排除其它血细胞减少的原因，如其它髓系肿瘤。
4. 不符合其它髓系肿瘤的诊断标准。
其诊断标准是：满足下列所有标准可诊断为意义不明的克隆性细胞减少症，如仅满足下列条件中的2和3条，可诊断为意义不明的特发性细胞减少(ICUS)
1. 骨髓或外周血可检出髓系肿瘤相关驱动基因突变，突变丰度 （VAF）≥2%（男性X连锁基因突变是VAF≥4%) ；或者髓系细胞克隆性染色体异常。
2. 患者有持续4个月以上的无明确原因的一系或多系细胞减少持续性细胞减少病史。
3. 骨髓检查不能满足髓系肿瘤诊断标。
分子标记：
髓系肿瘤相关的分子变异如下表
|
Gene Name |
Criteria for Classification as a Clonal Haematopoiesis Driver Mutation |
Reference Transcript |
|
|
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|
DNMT3A |
Frameshift/nonsense/splice-site; Missense in aa range: p.292-350, p.482-614 and p.634-912 |
NM_022552 |
|
TET2 |
Frameshift/nonsense/splice-site; Missense in aa range: p.1104-1481 and p.1843-2002 |
NM_001127208 |
|
ASXL1 |
Frameshift/nonsense/splice-site in exon 11-12 |
NM_015338 |
|
JAK2 |
p.V617F; Missense/indel in aa range: p.536-547 |
NM_004972 |
|
TP53 |
Frameshift/nonsense/splice-site; Missense in aa range: p.72, p.95-288 and p.337 |
NM_001126112 |
|
SF3B1 |
Missense in terminal HEAT domains (p.529-1201) |
NM_012433 |
|
PPM1D |
Frameshift/nonsense/splice-site in exon 5/6 |
NM_003620 |
|
SRSF2 |
Missense/in-frame deletion involving P95 |
NM_003016 |
|
IDH1 |
Missense at p.R132 |
NM_005896 |
|
IDH2 |
Missense at p.R140 or p.R172 |
NM_002168 |
|
U2AF1 |
Missense at p.S34 / p.R156 / p.Q157 |
NM_006758 |
|
KRAS |
Missense at p.G12 / p.G13 / p.Q61 / p.A146 |
NM_033360 |
|
NRAS |
Missense at p.G12 / p.G13 / p.Q61 |
NM_002524 |
|
CTCF |
Frameshift/nonsense/splice-site, p.R377C, p.R377H, p.P378A, p.P378L |
NM_006565 |
|
CBL |
Missense in Linker/RING finger domains (p.345-434) |
NM_005188 |
|
GNB1 |
Missense at p.K57 / p.G53 / p.I81 |
NM_002074 |
|
BRCC3 |
Frameshift/nonsense/splice-site |
NM_024332 |
|
PTPN11 |
Missense in aa range p.58-76 and p.491-510 |
NM_002834 |
|
GNAS |
Missense at p.R201 |
NM_016592 |
|
BCOR |
Frameshift/nonsense/splice-site |
NM_001123385 |
|
BCORL1 |
Frameshift/nonsense/splice-site |
NM_021946 |
|
Other |
|
|
|
BRAF |
Missense in aa range p.590-615; Missense at p.G469 |
NM_004333 |
|
CALR |
Frameshift in exon 9 |
NM_004343 |
|
CEBPA |
Frameshift/nonsense/splice-site |
NM_004364 |
|
CREBBP |
Frameshift/nonsense/splice-site |
NM_004380 |
|
CSF1R |
Missense at p.L301 / p.Y969 |
NM_005211 |
|
CSF3R |
T615A, T618I, truncating c.741-791 |
NM_000760 |
|
CUX1 |
Frameshift/nonsense/splice-site |
NM_181552 |
|
ETV6 |
Frameshift/nonsense/splice-site |
NM_001987 |
|
EZH2 |
Frameshift/nonsense/splice-site; Missense in SET domain (p.617-732) |
NM_001203247 |
|
GATA2 |
Frameshift/nonsense/splice-site, p.R293Q, p.N317H, p.A318T, p.A318V, p.A318G, p.G320D, p.L321P, p.L321F, p.L321V, p.Q328P, p.R330Q, p.R361L, p.L359V, p.A372T, p.R384G, p.R384K |
NM_001145661 |
|
JAK3 |
p.M511T, p.M511I, p.A572V, p.A572T, p.A573V, p.R657Q, p.V715I, p.V715A |
NM_000215 |
|
KDM6A |
Frameshift/nonsense/splice-site |
NM_021140 |
|
KIT |
ins503, p.V559A, p.V559D, p.V559G, p.V559I, p.V560D, p.V560A, p.V560G, p.V560E, del560, p.E561K, del579, p.P627L, p.P627T, p.R634W, p.K642E, p.K642Q, p.V654A, p.V654E, p.H697Y, p.H697D, p.E761D, p.K807R, p.D816H, p.D816Y, p.D816F, p.D816I, p.D816V, p.D816H, del551-559 |
NM_000222 |
|
KMT2A |
Frameshift/nonsense/splice-site |
NM_005933 |
|
MPL |
p.S505G, p.S505N, p.S505C, p.L510P, del513, p.W515A, p.W515R, p.W515K, p.W515S, p.W515L, p.A519T, p.A519V, p.Y591D, p.W515-518KT |
NM_005373 |
|
MYD88 |
p.L265P |
NM_002468 |
|
NOTCH1 |
Frameshift/nonsense/splice-site/missense in exon 26-34 |
NM_017617 |
|
PHF6 |
Frameshift/nonsense/splice-site |
NM_001015877 |
|
PIGA |
Frameshift/nonsense/splice-site |
NM_002641 |
|
PRPF40B |
Frameshift/nonsense/splice-site |
NM_001031698 |
|
PTEN |
Frameshift/nonsense/splice-site |
NM_000314 |
|
RAD21 |
Frameshift/nonsense/splice-site |
NM_006265 |
|
RUNX1 |
Frameshift/nonsense/splice-site, p.S73F, p.H78Q, p.H78L, p.R80C, p.R80P, p.R80H, p.L85Q, p.P86L, p.P86H, p.S114L, p.D133Y, p.L134P, p.R135G, p.R135K, p.R135S, p.R139Q, p.R142S, p.A165V, p.R174Q, p.R177L, p.R177Q, p.A224T, p.D171G, p.D171V, p.D171N, p.R205W, p.R223C |
NM_001001890 |
|
SETBP1 |
p.D868N, p.D868T, p.S869N, p.G870S, p.I871T, p.D880N, p.D880Q |
NM_015559 |
|
SF1 |
Frameshift/nonsense/splice-site |
NM_004630 |
|
SF3A1 |
Frameshift/nonsense/splice-site |
NM_005877 |
|
SMC1A |
Missense at R96 / R586 |
NM_006306 |
|
SMC3 |
Frameshift/nonsense/splice-site |
NM_005445 |
|
STAG2 |
Frameshift/nonsense/splice-site |
NM_006603 |
|
STAT3 |
Missense in SH2 domain (p.580-670) |
NM_139276 |
|
U2AF2 |
Missense in RNA recognition motifs domains (p.149-231, p.259-337, p.381-462) |
NM_007279 |
|
WT1 |
Frameshift/nonsense/splice-site |
NM_024426 |
|
ZRSR2 |
Frameshift/nonsense/splice-site |
NM_005089 |
预后：
参考文献：
