Results of sequential studies of mutations of ASXL1 and other genes in the patients with ASXL1 mutations at diagnosis and in the 2 patients (UPNs 55 and 56) acquiring ASXL1 mutations at relapse
| Case no. . | Interval, mo* . | Status . | Karyotype . | Mutation† . | |
|---|---|---|---|---|---|
| ASXL1 . | Others . | ||||
| 4 | Diagnosis | t(3;21;8) | + | c-KIT | |
| 4.9 | CR | N | − | ||
| 6 | Diagnosis | N | + | ||
| 6.8 | CR | ND | − | ||
| 7 | Diagnosis | t(16;21), +8 | + | NRAS | |
| 1.8 | PR | N | + | NRAS | |
| 1.4 | CR | N | + | NRAS | |
| 0.9 | CR | N | + | NRAS | |
| 3.3 | Relapse | N | + | NRAS | |
| 0.6 | Refractory | ND | + | NRAS | |
| 2.1 | Refractory | Complex | + | NRAS | |
| 12 | Diagnosis | del(7)(q22q36) | + | RUNX1, NPM1 | |
| 5.4 | CR | N | + | ||
| 2.4 | CR | N | + | ||
| 1.6 | Relapse | N | + | NPM1 | |
| 16 | Diagnosis | +i(11)(q10) | + | ||
| 8.2 | CR | ND | − | ||
| 1.6 | Relapse 1 | ND | + | ||
| 17 | Diagnosis | −X | + | FLT3-TKD | |
| 5.2 | CR | N | − | ||
| 21 | Diagnosis | t(8;21) | + | ||
| 6.7 | CR | ND | − | ||
| 23 | Diagnosis | del(12)(p11p13), −7 | + | RUNX1, PTPN11 | |
| 2.3 | CR | N | − | ||
| 24 | Diagnosis | t(8;21) | + | ||
| 1.6 | CR | N | − | ||
| 30 | Diagnosis | t(8;21) | + | c-KIT | |
| 1.2 | CR | N | − | ||
| 11.6 | Relapse | t(8;21), del(5)(q15q35) | −‡ | c-KIT§ | |
| 3.2 | Refractory | t(8;21), del(5)(q15q35) | −‡ | c-KIT§ | |
| 33 | Diagnosis | N | + | FLT3-TKD, RUNX1 | |
| 5.9 | CR | ND | + | RUNX1 | |
| 2.6 | CR | ND | + | RUNX1 | |
| 4.8 | Relapse | ND | + | FLT3-TKD, RUNX1 | |
| 40 | Diagnosis | t(8;21) | + | NRAS | |
| 4.3 | CR | N | − | ||
| 44 | Diagnosis | t(8;21) | + | ||
| 3.0 | CR | N | − | ||
| 48 | Diagnosis | t(9;11;13) | + | FLT3-TKD | |
| 0.9 | CR | N | − | ||
| 50 | Diagnosis | N | + | PTPN11 | |
| 4.4 | CR | ND | − | ||
| 51 | Diagnosis | add(5)(q22) | + | ||
| 1.7 | CR | ND | − | ||
| 53 | Diagnosis | −7 | + | FLT3-TKD | |
| 2.6 | PR | −7 | + | FLT3-TKD | |
| 10.6 | PR | −7 | + | ||
| 2.9 | CR | N | − | ||
| 4.2 | Relapse | ND | +∥ | ||
| 54 | Diagnosis | Complex | + | ||
| 1.5 | CR | ND | − | ||
| 55 | Diagnosis | t(15;17) | − | ||
| 11.9 | Relapse | t(15;17) | + | ||
| 56 | Diagnosis | N | − | CEBPA | |
| 21.7 | Relapse | del(9)(q13q32) | + | CEBPA | |
| Case no. . | Interval, mo* . | Status . | Karyotype . | Mutation† . | |
|---|---|---|---|---|---|
| ASXL1 . | Others . | ||||
| 4 | Diagnosis | t(3;21;8) | + | c-KIT | |
| 4.9 | CR | N | − | ||
| 6 | Diagnosis | N | + | ||
| 6.8 | CR | ND | − | ||
| 7 | Diagnosis | t(16;21), +8 | + | NRAS | |
| 1.8 | PR | N | + | NRAS | |
| 1.4 | CR | N | + | NRAS | |
| 0.9 | CR | N | + | NRAS | |
| 3.3 | Relapse | N | + | NRAS | |
| 0.6 | Refractory | ND | + | NRAS | |
| 2.1 | Refractory | Complex | + | NRAS | |
| 12 | Diagnosis | del(7)(q22q36) | + | RUNX1, NPM1 | |
| 5.4 | CR | N | + | ||
| 2.4 | CR | N | + | ||
| 1.6 | Relapse | N | + | NPM1 | |
| 16 | Diagnosis | +i(11)(q10) | + | ||
| 8.2 | CR | ND | − | ||
| 1.6 | Relapse 1 | ND | + | ||
| 17 | Diagnosis | −X | + | FLT3-TKD | |
| 5.2 | CR | N | − | ||
| 21 | Diagnosis | t(8;21) | + | ||
| 6.7 | CR | ND | − | ||
| 23 | Diagnosis | del(12)(p11p13), −7 | + | RUNX1, PTPN11 | |
| 2.3 | CR | N | − | ||
| 24 | Diagnosis | t(8;21) | + | ||
| 1.6 | CR | N | − | ||
| 30 | Diagnosis | t(8;21) | + | c-KIT | |
| 1.2 | CR | N | − | ||
| 11.6 | Relapse | t(8;21), del(5)(q15q35) | −‡ | c-KIT§ | |
| 3.2 | Refractory | t(8;21), del(5)(q15q35) | −‡ | c-KIT§ | |
| 33 | Diagnosis | N | + | FLT3-TKD, RUNX1 | |
| 5.9 | CR | ND | + | RUNX1 | |
| 2.6 | CR | ND | + | RUNX1 | |
| 4.8 | Relapse | ND | + | FLT3-TKD, RUNX1 | |
| 40 | Diagnosis | t(8;21) | + | NRAS | |
| 4.3 | CR | N | − | ||
| 44 | Diagnosis | t(8;21) | + | ||
| 3.0 | CR | N | − | ||
| 48 | Diagnosis | t(9;11;13) | + | FLT3-TKD | |
| 0.9 | CR | N | − | ||
| 50 | Diagnosis | N | + | PTPN11 | |
| 4.4 | CR | ND | − | ||
| 51 | Diagnosis | add(5)(q22) | + | ||
| 1.7 | CR | ND | − | ||
| 53 | Diagnosis | −7 | + | FLT3-TKD | |
| 2.6 | PR | −7 | + | FLT3-TKD | |
| 10.6 | PR | −7 | + | ||
| 2.9 | CR | N | − | ||
| 4.2 | Relapse | ND | +∥ | ||
| 54 | Diagnosis | Complex | + | ||
| 1.5 | CR | ND | − | ||
| 55 | Diagnosis | t(15;17) | − | ||
| 11.9 | Relapse | t(15;17) | + | ||
| 56 | Diagnosis | N | − | CEBPA | |
| 21.7 | Relapse | del(9)(q13q32) | + | CEBPA | |
The data of sequential studies on 107 patients without ASXL1 mutation both at diagnosis and at relapse were not shown in this table. Two (UPNs 55 and 56) of the 109 patients acquired ASXL1 mutation at relapse.
UPN indicates unique patient number; CR, complete remission; N, normal; ND, no data; PR, partial remission; and TKD, tyrosine kinase domain.
Interval (in months) between 2 consecutive studies.
All patients with ASXL1 mutations are heterozygous.
The ASXL1 mutation in this relapsed sample could not be detected by sequencing of polymerase chain reaction products but was detected in 1 of the 20 clones by TA cloning followed by sequencing of the individual clones. The mutation was not detectable by both direct sequencing and TA cloning in refractory status.
Mutation of c-KIT in these 2 samples was in exon 17, but the original c-KIT mutation in this patient was in exon 8.
This sample did not have original ASXL1 mutation but gained a new non-sense mutation of ASXL1.