Are Bcr-Abl KD mutations already detectable at the time ... - siesonline

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Results (II)Point mutations were randomly and uniformly distributedall over the KDMost of them were not likely to be clinically relevantP-loop C-helix SH3 contact SH2 contact A-loopP216P K245R Y257H E275E E292G T315I E334E I360T T392I Q477stopK222E G249S Y264C E281K I293T F317L V335V A366A H396PD223N G250RA288T V304I/A T319A N336D R367stop I403TG227G Q252stop V289A R307Q Y326Y A337A K378E W405CV228A Y253YL327L Y342Y A380A A407AS229T/P G254EA344T L384PC346stop T389TE352G/KY353YMutations that have been reported in imatinib-resistant pts are highlighted
N12345678910111213Status (time fromthe start ofdasatinib, mo)Relapsed (10)Relapsed (6)Relapsed (7)Relapsed (4)Relapsed (8)Relapsed (7)Relapsed (2)Relapsed (6)Remission (13)Remission (5)Remission (12)Remission (23)Remission (20)Results (III)Each In In two contrast, patients, had an the F317L evidence T315I detected observed of two at to diagnosis at twelve relapse different failed could to already mutations expandbedetected at the time of diagnosisSexMMMFFFFFFFMFMAge49565647745859305734527372Bcr-Abltypep190p210p210p190p210p210p210p210p190p190p190p210p190Mutations* at diagnosis (total no. of clones sequenced)L266P; A337A (150)K222E; V289A; V335V; K378E (180)V228A; R307Q; W405C (150)E275E; E281K; T319A; N336D (200)K245R; I293T; V304I; D363D; R367stop; K378E; 39 bp ins (180)G250R; L327L; I360T (150)G227G; I293T; V304I; T315I; C346stop; W405C (200)P216P; Y264C; T315I; A344T (150)D223N; S229T; Q252stop; L384P; T392I; A407A;del(cggga)1343 (200)S229P; K245R; A288T; 171 bp ins (200)G254E; Y326Y; E334E (150)E286E; E352K; A380A; T389T; Q477stop (150)G249S; Y253Y; Y257H; E292G; T304A; F317L; Y342Y; E352G;Y353Y; A366A; H396P; I403T (200)* Each mutation was detected by bidirectional sequencing in 2 to 5 independent clonesMutation atrelapse(direct seq)T315IT315IWTWTT315IE255KT315IT315IN.A.N.A.N.A.N.A.N.A.
Page 1 and 2: LAL:significato clinico e biologico
Page 3 and 4: Imatinib-resistant pts with Ph+ ALL
Page 5 and 6: Second-line TKIs in imatinib resist
Page 7 and 8: In ALL genetic instability is high
Page 9 and 10: Are Bcr-Abl KD mutations alreadydet
Page 11 and 12: Patients (II)NSexAgeBcr-Abl typeSta
Page 13: Results (I)Aberrant Bcr-Abl KD sequ
Page 17 and 18: Take-home messagesa) Bcr-Abl KD mut

Are Bcr-Abl KD mutations already detectable at the time ... - siesonline

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