Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc
Journal website http://www.jocmr.org

Original Article

Volume 8, Number 1, January 2016, pages 29-39

The Clinical Significance of IDH Mutations in Essential Thrombocythemia and Primary Myelofibrosis

Figures

Figure 1.
Figure 1. HRM curve analysis for IDH1 (R132) samples. The differential melting properties of wild-type and mutant type IDH1 (R132) using (a) normalized and temperature-shifted melting curves and (b) normalized and temperature-shifted difference plots. HRM curve analysis for IDH2 (R140) samples. The differential melting properties of wild-type and mutant type IDH2 (R140) using (c) normalized and temperature-shifted melting curves and (d) normalized and temperature-shifted difference plots. HRM curve analysis for IDH2 (R172) samples. The melting properties of IDH2 (R172) are shown using (e) normalized and temperature-shifted melting curves and (f) normalized and temperature-shifted difference plots. All samples of IDH2 (R172) showed the same pattern of melting temperature indicating that all patient samples are wild-type for IDH2 (R172).
Figure 2.
Figure 2. Survival outcomes and leukemia-free survival in PMF patients (n = 77). (a) Kaplan-Meier survival analysis of PMF patients with respect to IDH mutation status. OS was similar between patients with IDH mutations and those with no mutations (mean 125 months; 95% CI: 11 - 238 and 128 months; 95% CI: 98 - 157, respectively; P = 0.351). (b) Leukemia-free survival data for 77 PMF patients stratified by the status of IDH mutations. PMF patients with IDH mutations had shorter LFS compared to patients without IDH mutations (mean 169 months; 95% CI: 159 - 180 and 214 months; 95% CI: 95 - 332, respectively; P = 0.024).

Tables

Table 1. Clinical and Molecular Characteristics of IDH-Mutated PMF Patients
 
UPNAgeGKaryotypeIDHJAK2 (allele burden)FUOSDrugSurvival
UPN indicates unique patient number. G: gender; F: female; FU: follow-up (months); OS: overall survival (months). *Patient with leukemic transformation.
1*82FNormalIDH1 R132C(-)55HydroxyureaDeath
259FNormalIDH1 R132C(-)2424HydroxyureaDeath
386FNormalIDH1 R132C(+) (31-50%)187187HydroxyureaDeath
457FNormalIDH1 R132S(+) (5-12.5%)284284HydroxyureaAlive
537FNormalIDH2 R140Q(+) (31-50%)44HydroxyureaAlive

 

Table 2. Clinical and Molecular Characteristics of IDH-Mutated ET Patients
 
UPNAgeGIDHJAK2 (allele burden)FUOSDrugSurvival
UPN indicates unique patient number. G: gender; F: female; M: male; FU: follow-up (months); OS: overall survival (months).
155MIDH1 R132C(-)6464Hydroxyurea, ASAAlive
233FIDH2 R140Q(+) (5%)5260HydroxyureaAlive

 

Table 3. Clinical and Laboratory Features of PMF Patients Divided by IDH Mutational Status
 
PMFIDH mutant (mean (SD))IDH wild-type (mean (SD))P value
Number of patients572-
Age at recording64.2 (20)60.6 (14.2)0.642
Age at diagnosis55.4 (20.6)56.93 (14.1)0.86
Age at sampling63.2 (20.1)59.3 (14.02)0.679
Females (%)5 (100%)38 (52.8%)0.063
Total leukocyte at diagnosis (mm3)9.662 (5.725)14.892 (13.886)0.482
Hb at diagnosis (g/dL)10 (1.3)10.6 (2.2)0.482
HCT at diagnosis (%)31.4 (4.87)32.1 (7.13)0.694
Platelet count at diagnosis (mm3)272.760 (267.777)444.948 (366.701)0.193
LDH at diagnosis (U/L)713 (470)836 (390)0.251
Spleen size at diagnosis (mm)179.4 (30.7)198.9 (43.7)0.325
PMFIDH mutant, n (%)IDH wild-type, n (%)P value
Risk factors for cardiovascular diseases3 (60%)43 (59.7%)1
Splenomegaly group5 (100%)72 (100%)0.594
  No splenomegaly01 (1.4%)-
  Mild splenomegaly2 (40%)15 (20.8%)-
  Massive splenomegaly3 (60%)56 (77.8%)-
Bleeding3 (60%)12 (16.7%)0.048
Need for red blood cell transfusion1 (20%)20 (27.8%)1
Hydroxyurea5 (100%)67 (93.1%)1
History of splenectomy04 (5.6%)1
AHSCT03 (4.2%)1
ASA1 (20%)46 (63.9%)0.072
Leukemic transformation1 (20%)3 (4.2%)0.24
Death3 (60%)11 (15.3%)0.039
Thrombosis1 (20%)10 (13.9%)0.548
Thrombosis group5 (100%)72 (100%)0.802
  No thrombosis4 (80%)62 (86.1%)-
  Arterial1 (20%)6 (8.3%)-
  Venous03 (4.2%)-
  Arterial and venous01 (1.4%)-
JAK2V617F mutation3 (60%)55 (76.4%)0.592
JAK2V617F group5 (100%)72 (100%)0.401
  No mutation2 (40%)17 (23.6%)-
  Low allele burden3 (60%)37 (51.4%)-
  High allele burden018 (25%)-
Karyotype5 (100%)72 (100%)0.671
  Normal5 (100%)62 (86.1%)-
  Favorable07 (9.7%)-
  Unfavorable03 (4.2%)-
DIPSS-plus5 (100%)72 (100%)0.889
  Low risk1 (20%)14 (19.4%)-
  Intermediate-1 risk2 (40%)25 (34.7%)-
  Intermediate-2 risk2 (40%)25 (34.7%)-
  High risk08 (11.2%)-