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Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype Cover

Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype

Radiology and Oncology
Volume 50 (2016): Issue 4 (December 2016)
By:
Open Access
|Sep 2016

Figures & Tables

Impact of IDH mutation on overall survival (p = 0.039 by Kaplan-Meier method).
Impact of IDH mutation on overall survival (p = 0.039 by Kaplan-Meier method).
Overall survival associated with IDH mutations and allogeneic stem cell transplantation in AML-NK patients (p = 0.006 by Kaplan-Meier method).
Overall survival associated with IDH mutations and allogeneic stem cell transplantation in AML-NK patients (p = 0.006 by Kaplan-Meier method).
Comparison of the overall survival in intermediate group (NPM1-/FLT3-) between IDH+ and IDH-patients (p = 0.050 by Kaplan–Meier method)
Comparison of the overall survival in intermediate group (NPM1-/FLT3-) between IDH+ and IDH-patients (p = 0.050 by Kaplan–Meier method)

Results of sequential studies of IDH+ patients

Patient IDAge/ sexIDH/FLT3/NPM status on diagnosisDisease status after inductionIDH/FLT3/NPM status after inductionDisease status after consolidation therapyIDH/FLT3/NPM status after consolidationRelapseIDH/FLT3/NPM status in relapse
24553/FIDH2R140Q/wt/wtCRwt /wt/wtCR/yes/
IDH2R172K/
27550/FIDH2R172K/wt/wtCRwt /wt/wtCR/yesFLT3-D835/wt
28061/FIDH1R132H/FLT3-ITD/Type ARD//
/RD/
29138/FIDH2R140Q/FLT3-ITD/Type ARD/RD///
30547/MIDH2R140Qwt/wtCRwt /wt/wtCR/yes/
32040/MIDH2R140Wwt/wtCRwt /wt/wtCRwt /wt/wt//
IDH2R140L/
34939/MIDH2R140L/wt/wtCRwt/wtCRwt /wt/wt//
37866/MIDH1R132H/wt/Type AED/////
38044/FIDH1R132C/wt/wtCRyesIDH1R132C/wt/wt
CRwt /wt/wt/
39354/MIDH2R132C/FLT3-D835/wtCRwt /wt/wtCR/yes/
39923/FIDH2R140Q/wt/Type AED/////
40169/MIDH2R140Q/FLT3-ITD/wtRD/////
40373/FIDH1R132C/wt/wtRD/////
41246/MIDH2R140Q/wt/Type ARD/////
41862/FIDH1R132G/FLT3-ITD/Type ACRwt /wt/wtCR///
42343/MIDH2R140Q/wt/wtED/////
42656/MIDH2R172K/wt/wtED/////
IDH1R132C/
46963/MIDH1R132C/FLT3-D835/ Type ACRwt/wtCR/yes/
IDH2R140Q/
48773/MIDH2R140Q/wt/wtRDwt/wtRD///
55650/MIDH2R140Q/wt/Type AED/////
61230/MIDH2R140Q/wt/wtCRwt /wt/wtCRwt /wt/wt//
61540/FIDH2R140Q/wt/Type ACRwt /wt/wtCRwt /wt/wt//
64543/FIDH2R140G/FLT3-ITD/Type ARD/////
67233/FIDH1R132S/wt/Type ARD/////
68067/MIDH2R140Q/FLT3-D835/wtED/////

Clinical characteristics of patients with de novo AML-NK stratified by the presence or absence of IDH mutations

ParameterTotal (n = 110)IDH + (n = 25)IDH- (n = 85)p value
Sex0.617
Male (%)62 (56.4)13 (21)49 (79)
Female (%)48 (43.6)12 (25)36 (75)
Age, years, median (range)53.5(19-78)50(23-73)54(19-78)0.783
ECOG ≥20.081
Yes45(40.9)14(31.1)31 (68.9)
No65(59.1)11(16.9)54 (83.1)
HCT-CI ≥30.300
Yes8(7.3)3 (37.5)5 (62.5)
No102(92.7)22(21.6)80(78.4)
WBC count, x109/l (range)16.8 (0.5-195)6.9 (0.5-160)17.4 (0.8-195)0.373
Haemoglobin
median, range95.5 (6-178)100 (57-178)94 (6-140)0.810
Platelets (x109/L)
median, range68 (1-420)109(16-193)56 (1-420)0.024
LDH (U/L) median, range917 (273-7180)901 (315-5105)922.5 (273-7180)0.825
Peripheral blood blast (%)26 (0-96)60.5 (0-96)21 (0-96)0.031
Bone marrow blasts (%)71 (23-97)67 (33-97)73 (23-97)0.920
FAB (%)0.139
M0104 (40)6 (60)
M1226 (27.3)16(72.7)
M2319 (29)22 (71)
M4245 (21)19 (79)
M5221 (0.05)21 (95.5)
M610 (0.0)1 (100.0)
FLT3-ITD0.626
present (%)26(23.6)5 (19.2)21 (80.8)
absent (%)84(76.4)20 (23.8)64 (76.2)
FLT3-D8350.428
present (%)93 (33.3)6 (66.7)
absent (%)10122 (21.8)79 (78.2)
NPM10.496
present (%)42(38.2)11(26.2)31(73.8)
absent (%)68(61.8)14(20.6)54(79.4)

Type of IDH1 and IDH2 mutations identified in 110 AML-NK patients

MutationNucleotide changeAmino acid changeNo. of patients
IDH1
c.394C>TR132C4
c.395G>AR132H2
c.394C>GR132G1
c.394C>AR132S1
IDH2
c.419G>AR140Q12
c.418C>TR140W1
c.419G>TR140L1
c.418C>GR140G1
c.515G>AR172K2
DOI: https://doi.org/10.1515/raon-2016-0044 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099
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Language: English
Page range: 385 - 393
Submitted on: Mar 28, 2016
Accepted on: Jun 18, 2016
Published on: Sep 8, 2016
Published by: Association of Radiology and Oncology
In partnership with: Paradigm Publishing Services
Publication frequency: 4 times per year
Keywords:
mutations,
mutations,
acute myeloid leukaemia,
normal karyotype
Related subjects:
Medicine,
Clinical medicine,
Internal medicine,
Haematology, oncology,
Radiology

© 2016 Marijana Virijevic, Teodora Karan-Djurasevic, Irena Marjanovic, Natasa Tosic, Mirjana Mitrovic, Irena Djunic, Natasa Colovic, Ana Vidovic, Nada Suvajdzic-Vukovic, Dragica Tomin, Sonja Pavlovic, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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