Table 1.

Frequency of FLT3 mutations in hematologic malignancy in adult AML, ALL, and MDS

PhenotypeCasesMutation (%)CommentsReference
Adult AML/ALL/MDS     
  1 AML 30 5/30 (17) ITD  Nakao et al 199681 
    ALL 50 0/50 (0) ITD   
  2 MDS 58 2/58 (3) ITD 4/7 also had N-RAS or p53 Horiike et al 199782 
  5/34 (15) ITD 6/7 had abnormal karyotype  
  3 APL 74 15/74 (20.3) ITD Correlates with high WBC Kiyoi et al 199783 
  4 AML 112 22/112 (20) ITD  Yokota et al 199784 
    ALL 55 0/55 (0) ITD   
    MDS 37 1/37 (3) ITD   
  5 AML 429 30/429 (7) activation loop D835Y 22/32 (69%) Yamamoto et al 200190 
    MDS 29 1/29 (3) activation loop D835V 5/32 (16%)  
    ALL 36 1/36 (8) activation loop D835H 1/32 (3%)  
   D835E 1/32 (3%)  
   D835N 1/32 (3%)  
  6 AML 97 7/35 (7.2) activation loop D835Y 5/7 Abu-Duhier et al 2001103 
   D835H 1/7  
   D835del 1/7  
  7 Elderly AML 140 47/140 (34) ITD Associated with high WBC,
high blast, normal cytogenetics 		Stirewalt et al 200186 
  [28/140 (19) RAS]†   
  [13/140 (9) p53]    
  8 AML (APL excluded) 201 43/201 ITD  Kiyoi et al 199995 
  25/201 N-RAS   
  3/201 FLT3 + RAS   
  9 AML 81 18/81 (2.2) ITD  Rombouts et al 2000121 
 10 AML, de novo 103 14/113 (13.2) ITD  Abu-Duhier et al 200094 
 11 AML 854 231/854 (27) ITD Correlates with high WBC, blasts Kottaridis et al 2001100 
 12 AML 82 23/82 (28) ITD  Whitman et al 2001101 
  Lower than 60, de novo  8/23 loss residual allele   
  Normal cytogenetics     
 13 AML 161 11/161 (6.8) activation loop 4/10 inv(16) Nomdedeu et al 2001135 
   1/10 t(9;11)  
 14 AML 37 17/37 (45.9) FLT3-ITD  Nomdedeu et al 2001135 
   Normal  4/37 MLL partial tandem duplication (PTD)   
   Karyotype  2/37 both MLL PTD and FLT3-ITD   
 15 AML 713 144/713 (20.2) ITD Higher ITD in M5 Frohling et al 2001123 
  54/713 (8.1) activation loop Lower ITD in M2  
    RAEB-T 18 1/18 (5.6) ITD
1/18 (5.6) activation loop  		13/713 had both ITD and activation
loop mutation 		 
   t(15;17) (34.4)  
   t(6;9) (88.9), n = 9  
 16 AML 188 49/188 (26) ITD 3.4% normal cytogenetics Frohling et al 2001123 
Pediatric AML   t(15;17) (50%)  
  1 AML 94 12/94 (13.8) ITD  Xu et al 199987 
    ALL 60 2/60 (3) ITD   
    MDS 32 0/32 (0)   
    JMML 15 0/15 (0)   
  2 AML 94 5/94 (5.3) ITD  Iwai et al 1999150 
  3 AML 64 7/64 (11) ITD High WBC Kondo et al 199992 
  4 AML 91 15/91 (16.5)  Meshinchi et al 200089 
  5 AML 56 17/56 (30.4) 7/11 M3 (63.6%) vs 10/44 other (22.7%) Arrigoni et al 2000143 
  6 Infant ALL 23 4/23 activation loop (22)  Armstrong et al 2001151 
Others     
 CML 20 0/20 ITD or D835 Baldwin et al 200198 
 NHL 30 0/30   
 Adult T-ALL 14 0/14   
 CLL 15 0/15   
 Multiple myeloma 38 0/38   
 Medulloblastoma 22 0/22   
 Epepdymoma 11 0/11   
 Oligodendroglioma 8 0/8   
 Glioblastoma multiforme 23 0/23   
 Anaplastic astrocytoma 1 0/1   
 Pilocytic astrocytoma 7 0/7   
 Acoustic neuroma 5 0/5   
 Breast 11 0/11   
 Head and neck 30 0/30   
 Lung 30 0/30   
 Prostate 92 0/92   
 Bladder 20 0/20   
 Thyroid 15 0/15   
 Child endodermal sinus 5 0/5   
 Dysgerminoma 6 0/6   
 Adult endodermal sinus 13 0/13   
 Mixed germ cell 3 0/3   
 Immature teratoma 5 0/5   
PhenotypeCasesMutation (%)CommentsReference
Adult AML/ALL/MDS     
  1 AML 30 5/30 (17) ITD  Nakao et al 199681 
    ALL 50 0/50 (0) ITD   
  2 MDS 58 2/58 (3) ITD 4/7 also had N-RAS or p53 Horiike et al 199782 
  5/34 (15) ITD 6/7 had abnormal karyotype  
  3 APL 74 15/74 (20.3) ITD Correlates with high WBC Kiyoi et al 199783 
  4 AML 112 22/112 (20) ITD  Yokota et al 199784 
    ALL 55 0/55 (0) ITD   
    MDS 37 1/37 (3) ITD   
  5 AML 429 30/429 (7) activation loop D835Y 22/32 (69%) Yamamoto et al 200190 
    MDS 29 1/29 (3) activation loop D835V 5/32 (16%)  
    ALL 36 1/36 (8) activation loop D835H 1/32 (3%)  
   D835E 1/32 (3%)  
   D835N 1/32 (3%)  
  6 AML 97 7/35 (7.2) activation loop D835Y 5/7 Abu-Duhier et al 2001103 
   D835H 1/7  
   D835del 1/7  
  7 Elderly AML 140 47/140 (34) ITD Associated with high WBC,
high blast, normal cytogenetics 		Stirewalt et al 200186 
  [28/140 (19) RAS]†   
  [13/140 (9) p53]    
  8 AML (APL excluded) 201 43/201 ITD  Kiyoi et al 199995 
  25/201 N-RAS   
  3/201 FLT3 + RAS   
  9 AML 81 18/81 (2.2) ITD  Rombouts et al 2000121 
 10 AML, de novo 103 14/113 (13.2) ITD  Abu-Duhier et al 200094 
 11 AML 854 231/854 (27) ITD Correlates with high WBC, blasts Kottaridis et al 2001100 
 12 AML 82 23/82 (28) ITD  Whitman et al 2001101 
  Lower than 60, de novo  8/23 loss residual allele   
  Normal cytogenetics     
 13 AML 161 11/161 (6.8) activation loop 4/10 inv(16) Nomdedeu et al 2001135 
   1/10 t(9;11)  
 14 AML 37 17/37 (45.9) FLT3-ITD  Nomdedeu et al 2001135 
   Normal  4/37 MLL partial tandem duplication (PTD)   
   Karyotype  2/37 both MLL PTD and FLT3-ITD   
 15 AML 713 144/713 (20.2) ITD Higher ITD in M5 Frohling et al 2001123 
  54/713 (8.1) activation loop Lower ITD in M2  
    RAEB-T 18 1/18 (5.6) ITD
1/18 (5.6) activation loop  		13/713 had both ITD and activation
loop mutation 		 
   t(15;17) (34.4)  
   t(6;9) (88.9), n = 9  
 16 AML 188 49/188 (26) ITD 3.4% normal cytogenetics Frohling et al 2001123 
Pediatric AML   t(15;17) (50%)  
  1 AML 94 12/94 (13.8) ITD  Xu et al 199987 
    ALL 60 2/60 (3) ITD   
    MDS 32 0/32 (0)   
    JMML 15 0/15 (0)   
  2 AML 94 5/94 (5.3) ITD  Iwai et al 1999150 
  3 AML 64 7/64 (11) ITD High WBC Kondo et al 199992 
  4 AML 91 15/91 (16.5)  Meshinchi et al 200089 
  5 AML 56 17/56 (30.4) 7/11 M3 (63.6%) vs 10/44 other (22.7%) Arrigoni et al 2000143 
  6 Infant ALL 23 4/23 activation loop (22)  Armstrong et al 2001151 
Others     
 CML 20 0/20 ITD or D835 Baldwin et al 200198 
 NHL 30 0/30   
 Adult T-ALL 14 0/14   
 CLL 15 0/15   
 Multiple myeloma 38 0/38   
 Medulloblastoma 22 0/22   
 Epepdymoma 11 0/11   
 Oligodendroglioma 8 0/8   
 Glioblastoma multiforme 23 0/23   
 Anaplastic astrocytoma 1 0/1   
 Pilocytic astrocytoma 7 0/7   
 Acoustic neuroma 5 0/5   
 Breast 11 0/11   
 Head and neck 30 0/30   
 Lung 30 0/30   
 Prostate 92 0/92   
 Bladder 20 0/20   
 Thyroid 15 0/15   
 Child endodermal sinus 5 0/5   
 Dysgerminoma 6 0/6   
 Adult endodermal sinus 13 0/13   
 Mixed germ cell 3 0/3   
 Immature teratoma 5 0/5   

RAEB-T indicates refractory anemia with excessive blasts in transformation; WBC, white blood cell count.

*

All D835 substitutions are constitutively activating tyrosine phosphorylated and confer factor independent growth to 32D cells.

†

2/47 with FLT3 also had RAS mutations.

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