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616-006-053.2-07-08 . 3 . . 2. ...

-- [ 2 ] --

L1, L2, L3 ( FAB, 1976 .) * L1 L2 L , , , , , , , , , , , , , , , , - - , , L1 L2 , , . 9.

(scoring system) L1 L2 ( FAB, 1981 .) 75 % + 20 % 25 % 20 % 75 % + 25 % - 20 % - : , 50 % , - : L1 : - 0 +2;

L2 : - -1 -4.

F A B [93] , .

. , , , , F A B - (intermediate) , (indeterminate). , . , FAB, , ( 0 ).

, , (, , ) (. . 14, 15). , . F A B 3 % + / + . - , + . , P A S - (. . 16) , [14]. . 10.

+ PAS (-) - : + - ;

- - ;

-(+) .

, -, -, -, -. : -, , - [ 1 4, 8 1 ].

, , : - - , - - , [53]. . 11 .

- - : C D 1 9, C D 7 9 a, CD22. , - - T d T ( - ), - II H L A - D R. C o m m o n - B - C A L L A - C D 1 0. - IgM ( - ). IgM ( s l g M ).

(EGIL, 1995) [53] CD19+ / CD79a+ / CD22+ - ( ).

TdT+ ( ), HLA-DR+ - - Common-B CD10+ - lgM+ s + CD3+ ( ) - TdT+, HLA-DR-, CD34 - CD7+ - CD2+ / CD5+ / CD8+ CD1a+ CD3+, CD1a ( ) -TCR /+ /8+ ( ) -TCR /5+ ( ) , , , , . .

- ( L1 L2 F A B - ) . , , , , , , . . ( 2 5 % ).

- ( . 17) 1,5 (51 %) 10 (13 % ), 1,5-10 (6 % ) [95, 9 6 ]. - [ 5 9 ].

MLL.

5" 10 ' IO IO 1Q 2 3 io io 1 I0 I0 I0 7 in IO IO IO IO 1 3 4 3 2 M n n H l i G I l FIT m:. I i n CDJ FITC D45 F I T C [ - " III" 10 I IT IO IO 3 1 IO IO 10 10 IO IO IO 1 2 "0 10 IB 10 IO 2 3 0 1 2 3 CD20 F I T C a io" O IO III III ~o io' I O 1 2 3 IO IO IO IO IO IO IO 3 2 3 2 3 (iujFTTC 09 I'B if a U.

* IO I I IO IO IO IO 200 400 600 00 IIWKI 2 1 2 3 TiiT FITC ز M.,-lopimdrlMPOlFITC FSr-lki|hl . 17. :

CD19+, CD20-, CD22+, CD10-, slgM-, CD34+, HLA-DR+, TdT+, CD79a+, cylgM - -, - - (. 18) 6 0 - 7 0 % [95, 9 7 ]. - , C D 1 0.

cylgM slgM. t(9;

22)(q34;

q11) t(12;

21)(p13;

q22), BCR/ABL TEUAML1, [98]. [99|.

" " i f ft b - 5~ % si iJ == io' ( " 10 = "" 2 3 4 2 IO IO IO "I," III IO III 2 IO IO 1 2 3 IO IO IO IO TM5 FITC M i IfCil FITC CD4 F I T C C03 FITC % "fe "= h jl a a E = 6 _ m % 10 To" in io' 3 4 1 2 *I0 10 lt IO IO IO II 111* 2 4 2 IO IO I Iff IO CDIOFIH CD7 FITC t'DIS FTTl II.' % ~b !l h a f;

W ~~ ~s = % t 10 4 V " in r 1 "In" io io io I 1 IO IO To" III III III I 2 3 * io' IO ( IIIVHK CDIaFITC. t I** e 3" 2 ~b _ s = =c *?o io' IO IO IO " io' 2 3 1 ;

a IO I IO 1 2 IO IO IO 2 1 1 FFTC V n n - M v. - I. p r f. n i. l j -. i M I t )i mi q lM 18. .:

CD19+. CD20+/-. CD22+. CD10+, slgM-, CD34+/-, HLA-DR+, TdT+, CD79a+, cylgM-.

- -. common-B - (. 19) 25 % [96]. - c y l g M slg X. 9 5 % - C D 1 0 T d T, 2/3 C D 3 4. C D 2 0 - [ 1 0 0 ]. - - , , - 1, 1 6 5 1. 2 0 - 2 5 % - t ( 1 ;

1 9 ) ( q 2 3 ;

p 1 3 ) d e r ( 1 9 ) t ( 1 ;

1 9 ) ( q 2 3 ;

p 1 3 ) 2/1. CD19+,CD10+,CD9+ C D 2 0 C D 3 4 100 % .

z "= IE .* io" 10' 10' To" lo io' ' IO IO IO 2 3 IO IO IO IO IO 2 3 2 3 IO M M H lC.I. F I T C CD45 F I T C CM FITC FITC " 10 to To in in in in 0 0 1 2 3 ~io IO IO III IO 1 2 3 IO I IO 1 2 3 CD20 FITC C D 7 FITC CD 1 0 FITC = 1o To io' io io io 7o io' 0 2 3 4 10' 10 IO 2 IO IO IO 2 3 I I 2 CD2 FITC CDI9FITC 'o - "b It " I! "o 10 To io 0 2 0 0 4 0 0 6 0 0 8 0 0 IO IO IO 2 10' 10' IO I -1 Ѳֲ.1 cy l M Vim M clopcroii JUT' I M I'l 1 I I 1 . 19. .:

CD19+, CD20+/-, CD22+, CD10+, slgM-, CD34+/-, HLA-DR+, TdT+, CD79a+, cylgM+.

- -, - 1 % - , , -, - . CD79a, CD79b, CD10, TdT, CD34.

- . - L1 L2 , t(8;

14), t(8;

22) t(2;

8), . - , - 1. 1 6. , .

- ( ) ( L 3 F A B - ) (. 20) 2-4 % slgp, - - [100] \ "I t " i f 9*-? ~I0 IO io w io' ~0 II)' IO IO IO io' 1 2 3 2 3 IO IO IO 2 3 CMS H .. H. I I 111 CO* FITC ' - r s " " lo" To" IO III III .0' IO IO 1 1 3 ' io io 2 3 2 IO IO IB 1 2 3 CD20HK CDIOFITC CD7 FITC C U M FITC TB5TJ ' h -;

f W 3 To \p IO IO ID IO ~0 IO IO IO IO to" 1 2 3 4 1 2 3 10' 10

10* X?

CD2 F I I C " ' .

I I h 0_ ' Io It ID I* IO IO IO 1 200 400 MM W 2 3 4 2 3 ! It c.l M I III M i l Forvard Scatter MPOMIC f . 20 .:

CD19+, CD20+, CD22+, CD10+/-, slgM+, CD34-, HLA-DR -, TdT-, CD79a+, cylgM+/-. - - . , , L F A B - , - c o m m o n - B , CD19, CD22 CD10 T d T C D 3 4. , - , (, ) [101]. 8 , :

t(8;

14)(q24;

q32), t(2;

8)(p12;

q24) t(8;

22)(q24;

q11).

L1 L2 , T d T CD34, C D 2 0 slg [ 1 0 2 ]. .

, i "To" io io io io 1 2 3 " ' io io,,' 2 I IO* IO io" IO IO IO IO 1 2 1 2 3 CD4FT PC CD-IS FfTC f TO F I T C M O U M I k G I FITC "To io' io 0 IO IO IO IO IO IO IO IO 2 ~0 ~0 IO IO IO IO 1 2 3 2 3 4 1 2 3 CD7 F I T C CD20 F I T C ( 1134 F I T C I I )l mL IO IO IO IO 1 2 3 0' IO 10 2 3 CD2 FITC C D 10 F I T C "io" IO IO IO IO 1 2 3 IO IB IO 2 3 IO IO IO III 0 200 400 600 800 1000 "o 1 2 3 tnli-Mydopcroiiilue O l F O l KITI cy I g M FSC-llciBhl TdT F I T C . 2 1. .:

CD2+/-, CD3-, CD4-, CD8+ -,CD5-, CD7+, TdT+, CD1a-, CD34+.

- - (- ) - C D 3 ( ). T d T HLA-DR . - (- ) C D 7 (. 21). - - : C D 2, C D 5 C D 8 (. 22).

- C D 1 a ( 23).

\ \ h 1* I * "io" io' in IO IO 2 ~ IO IO IO I0 To io' IO IO IO 1 2 3 4 0 2 3 CD) FITC CD-I Mu.cl|i;

i FITC I A 8 io' io io io 7o 2 3 7o Io" IO IO IO 1 2 3 10' IO IO ' 2 CDIOFITC I ii:iniii C O M FITC C D 7 FITC - io 10" IO IO 2 m. 2 7o IO 10 III 10" 1 2 CD2 FITC ilgM F I I C C D I 9 FITC Q 2.

IKI 400 ( 800 io * ~0 IO IO IO IO 1 1 2 3 1 IO IO 3 forward Scjltft Vnli-4)cloperoiiduc(̲ײ 1 1 I I cv I g M rdTFIIC . 22. .:

CD2+, CD3-, CD4-, CD8-/+, CD4+-CD8+ -, CD5+, CD7+, TdT+, CD1a-, CD34+/-.

- - (pre- ) h ~o io' I O I* ~o 3 To I IO IO 2 3 IO IO IO IO IO IO IO 1 2 1 3 3 I, C I D45 H T f cm t ' \ "o lo 7o io IO IO IO IO III IO IO 7o I IO IO IO IO ID IO 1 2 3 1 2 3 1 2 3 1 2 CHfflTM CDllrTTC ( 1)7 H I T ~o io' 10 10' 10* 10 IO IO IO 7o io' io io 2 3 4 IO rjM DUFTTC CD2 IT I I- It s I?

L 7o io' io io io 2 3 7o" io' I IO IO 7 2 3 IO It IO IO 1 2 3 \ili-4\rioprrniidaMl4rOl M i l 400 600 NO 10 ol,M \4 llmbl . 23. .:

CD2+. CD3-. CD4-, CD8-, CD4+CD8+ +. CD5+, CD7+, TdT+, CD1a+, CD34+/-.

- - ( -) - . - - T C R 1 4 q 1 1. 2. 7 q 3 5 - 7 1 4 - 1 5 [ 1 0 4 ].

- ( L 1 L2 F A B ). - .

(85-90 %) , , [14]. , , , , , [103], ( 2 5 % ).

- .

(46 ). 5-8 % , . 58 % [105] (30) ( 1 % ), 25 % , [ 1 0 6 ].

, . . 4 6, X X 4 6, X Y, 30 % (. 24) [107], ( ) 4 0 % [ 1 0 8 ]. , , [109] II II II * ft 2 ft i t S 7 ** * ػ a 6 Ifl 1 IS 1. - - . 24 ., 12 .

-, - : 46,XY ( 4 7 - 5 0 ) ( 25). 8 15 %. , 10 , , . [110], [ 1 1 1, 1121.

II ix 3 M II II II 7 IB A1 AS * ft ft t ta is 1 14 f J| ft * 1I 19 X . 25. ., 1 . -, - . (47-50 ): 48., +, + ? 1 1 2 3 . S I in st 6 7 9 IB 11 I I M I II M MM ) M R 13 16 1? IB * II 19 2B 21 22 X . 26. ., 8 . -. common-B . (50 ):

58,,-,-1,-2,-3,-5,-9,-11,-12,-13+14,-15,-16,+18, -19.-20.+21,- (5165 ) 2730 % 210 (. 26). c o m m o n B 1010 /. : 7 2 8 6 %. [ 1 0 8, 110|. , t(9;

22), t(4,11) i(17q). in situ [ 1 1 0 ].

(65) ҭ [113].

. 12.

[114] / , % 2 3 1q23/PBXJ 1913.3/2 t(1;

19)(q23;

p13.3) 5-6 Pre-B (90 %) t(9,22)(q34;

q11.2) 3-5 - (90 %) 0q34MBl 22q11 2/BCf?

t(4H1)(q21;

q23) 2 pre-B (80 %) Aq2MAF4 11q23/MU 1 pre-B 11q23/M/.L t(1;

11)( 32;

q23) ip32/AF1P P t(9:11)(p22;

q23) 1 pre-B 9p22IAF9 11q23/M/.i.

pre-B:

t(11;

19)(q23;

p13.3) 1 Hq23/MU. 19P13.3/NL - t(5|14)(q31;

q32) 1 5q31/0 14q32//6H t(17;

19)(q22;

p13.3) - 17q22/HLF 1913.3/2 21q22MMLf t(12;

21)(p13;

q22) 1 -, - 12p13/TE/.

t(9;

12)(q34;

13) 1 -, - 9q34/ASL 12p13/T/.

P del(6q) 4-13 7-12 9p22/pf6 (MTS1) I(9p;

V);

del(9p) 3-5 11q23MX t(11q23;

V);

del(11q) I(12p13,V);

del(12p) 10-12 1213/(. t(8;

14)(q24.1;

q32) 3 (90 %) 8q24.1/MVC 14q32/7GH t(2;

8)( 12;

q24.1) 1 (4-5 %) 2p12//GK 8q24 IMYC P I(8;

22)(q24.1;

q11.2) 1 (6-10 %) Bq24.VMYC 22q11.2//GL 14q112ITCFWD t(11;

14)(p13;

q11.2) - (7 %) t(11;

14)(p15;

q11.2) - (1 %) 11p15/R8T/VJ :4q-\'\2/TCRAID 10q24/HOX7j t(10;

14)q(24;

q11.2) 1 - (5-14 %) 14q 11.21TCRA/D - (2 %) 8q24.1 IMYC t(8;

14)(q24.1;

q11.2) 1 14q112ITCRA/D . 1 2 3 t(1;

14)(p32-p34;

1 - (3%) 132-34// 14q11.2/TCRA/D q11.2) t(1;

14)(p34;

q11.2) 1 - 134/(_ 14q11.2/TCR/VD inv(14)(q11.2q32) and 1 - I4q11.2/TCRA/D 14q32//GH t(14;

14)(q11.2;

q32) t(1;

3)(p32-p34;

p21) 1 - 132-34/7, 3p2MTCTA t(1;

7)(p32;

q34-35) 1 - 132-34/7, 7q34-35/TCR t(1;

7)(p34;

q34-35) 1 - 1 34/1 7q34-35/TCR t(7;

9)(q34-35;

q34) 1 - 7q34-35/TCR8 9q34ITAN t(7;

9)(q34-35;

q32) 1 - 7q34-35/TCRB 9q32ITAL t(7;

10)(q34-35;

q24) 1 - 7q34-35/TCR8 \0q24IHOX t(7;

11)(q34-35;

p13) 1 - 11p13IRBTN 7q34-35/7"CR inv(7)(p15q34-35) 1 - 7p15/TCRG 7q34-35/ TCRB I(7;

19)(q34-35;

p13) 1 - 7q34-35/TCR8 19p13/i./LJ , , - ( . 13).

- [14] t(9;

22)(q34;

q11.2) BCR/ABL t(4;

11)(q21;

q23) AF4/MLL t(1;

19)(q23;

p13.3) /2 t(12;

21)(p13;

q22) TEUAML MLL, 11q23, , , . 2 8 % [ 1 1 5 ]. 6 0 - 7 0 % [ 1 1 6 ] 15 % [ 1 1 7 ]. MLL , 4 3 1 k D a. , , , .

30 MLL t(6;

11), t(9;

11), t(10;

11), t(11;

19), del(11)(q23), der(11)(q23) ., [ 1 1 2, 1 1 8 - 1 2 0 ]. t(4;

11)(q21;

q23) ( 1 2 3 :i II )l 1$ 11 IB || i'l ʲ 16 17 13 ' l ** V 21 22 X VI . 29 ., 4 . -, - : 46,XY,t(11:19)(q23;

p13) 1) 1 II *׻ I 7 8 IB II ft 1 II 1 i I 16 17 19 21 22 X 2 30 ., 2 . -. - : 46.XY, t(9;

11)(p22;

q23) t ( 9 ;

2 2 ) ( q 3 4 ;

q 11) (. 31), ( - ). 100 % , 3-5 % 1 % [ 1 2 3 ]. ( ) BCR/ABL (. 32). [124].

II { II z 1 S II II II II tl (t 7 ) 1* 11 * ft * 1 II 13 IS 1 17 l-l * 14 20 21 22 X . 31 ., 5 . -, - : 46,XX,t(9:22)(q34;

q11) + I 2 . 32 BCR/ABL : + - ( 562);

1 - ?//_- : 2 3 - 8///_- BCR;

- 7 0 % P h * BCR 2 2 - -bcr, 1 9 0 , - M-bcr, 2 1 0, . 1 9 0 210 , | 1 1 5 |. BCR/ABL G R 8 2, BCR/ABL R A S - [ 1 2 5 ]. BCR/ABL , BCL2 [ 1 2 6 ] . BCR-ABL [ 1 2 7, 128], , [127] BCR/ABL , - , . , 20 30 % 137, 99, 123, 1 2 9 - 1 3 3 ]. , [132-133] t ( 1 ;

1 9 ) ( q 2 3 ;

p 1 3 ) 5-6 % . 2 5 % - t(1;

19)(q23;

p13), 75 % - - d e r ( 1 9 ) t ( 1 ;

1 9 ) ( q 2 3 ;

p 1 3 ) (. 33) [ 1 1 2 ]. t ( 1 ;

1 9 ) ( q 2 3 ;

p 1 3 ) 2 19 1 1 2/1 (. 34), t ( 1 ;

1 9 ) ( q 2 3 ;

p 1 3 ) pre-B (clg+) ( 2 0 - 2 5 % ), C D 10. C D 1 9, C D 9 C D 3 4 1 % pre-B (clg-) - t(1;

19) , 5-10 % , t(1;

19) , , , 1112, 115, 1 2 0 | ! II \ 1 2 4 S ij 8 ! * 4 7 9 11 i * lb 13 14 IS 17 1 1I . - 19 . 33. X., 5 . -, - : 46, XX, der(19), t(1;

19)(q23:p13) 2-1 1 2 - + . 34. 2/1 : 1 2 - , 2-1: - ;

+ - t ( 8 ;

14) (. 35) 1-3% . L3 , . 11341. , 8 q 2 4 IGH 14q32. 10 15 % - , : t ( 2, 8 ) ( p 1 2 ;

q 2 4 ) t ( 8 ;

2 2 ) ( q 2 4 : q 1 1 ) [ 1 3 4 ]. - t(8;

14) .

( 80 %) ( 1 3 0 ].

S 1 9 * II - - 7 * II % fi "\ 13 17 ft * * 9 * 20 X V 19 21 . 35. ., 13 .

-: 46,XY.t(8;

14)(q24;

q32) t(12;

21) , . (FISH, ) , 16-32 % 1135-137] (. 36). c o m m o n - B - , 1 10 (70-80 % 3-6 ), , (124, 136, 138-140]. C D 1 3 C D 3 36. t(12;

21)(p13;

q22) FISH ( ) t(12;

21) TEL (12 ) AML1 (21 ) TEUAML1 (. 37) [ 1 2 4, 1 3 6, 1 3 7 ]. t ( 1 2 ;

2 1 ) ( p 1 3 ;

q 2 2 ) , AML1, , - . TEUAML^- TEL. TEL , TEL , . TEL .

TEUAML1 . TEL PDGFpR. c-ABL JAK2 - [ 1 4 1 ], T E L / A M. 7 - TEL, AML1 ( Lck, , - , 1, T C R, -3), [142].

- T C R 14q11.2, 7q35, 714-15, (8q24.1), TAL1 (132), RB77V7(1115), RBTN2 (1113), 11 (10q24), LCK (134.3-35). 30 % del(9p), - CDKN2A. - .

I 2 3 . 37. TEL/AML1 :

1-3 - TEL/4/VfL 7- ;

- S I L / T A L 1. SCL (TAL1, TCL5) 30 % - . TAL1 (3 % ), 90 . (26 %) [143]. TAL1, , , . . 132 TAL1 SIL SIUTAL1 (. 38).

I 2 3 -/* |. . 38. SIL/TAL1. SIUTAL 7- (1-4) - SIUTAL1;

- SIL V ( D ) J , , 98 % . TAL1 . 5 / / _ / 7 7 - , , , [ 1 4 3 - 1 4 6 ]. TAL1 S/L, -, TAL1. 2, TAL1 - , 2 - [147] SIL/TAL1 , [145].

, , [148].

, , , , , - .

, , , . , , . , , .

62 % . . . , - . 57 % . 30 % .

, . 10-13 % . .

.


4 3 % . 32 % . . ( 2 % ) 6-8 , , - [ 1 4 9 ]. [150].

24 % . , , , .

1 8 % , . . (IR0,68). , [149].

. 0,5 . : - - - - . , . . 30 % ( 0, 8 1,0 ) - , . . [150]. 1,2 . .

, ( 62 43 % ) ( 24 18 % ).

. 30 % .

.

1. ., 2 . (L2 F A B - ), - . . : (+4 ), (+5 ), (+0,5-1 ) ;

;

1,4 , - 1,2 (, 39).

) . 39. : ) : , ;

) :

, ;

) : 1,4 , 2. ., 17 . (L2 F A B - ), - 15+. .

: ( + 1 0 ), ( + 5 );

- 1,2 ;

: , 1,6 (. 40).

) ) ) . 40 : ) : , ;

6) :

;

ej : 1,2 ;

) : , ;

) : 1,6 3. , 11 . (L1 F A B - ), - . . : (+2,5-3 ), ;

;

1,6 , - 1,7 ( 4 1 ).

= ) . 41 ;

, ) ;

, ;

) Zoom - ;

) - 4 ., 4 . (L1 F A B - ), - 13+. + . : (+1), ( + 1 ) ;

;

(. 42).

) . 42. : ) : , ;

) : , ;

) : S- 5. ., 11 . (L2 F A B - ), - 1 0 +. : ;


, , ;

( 1,4 ), ( 1,2 ), - 1 ;

(. 4 3 ) ) ) . 43. : ) ;

, ;

, ;

6) :

, ;

) : - : ) :

, ;

) , ;

) : , , , , [151-155].

(5-10 % ), , (1-2 %) , - , / .

- ( 4 4 ;

4 8, ;

5 1, ).

. 44. - ., 13 ( - ). , , / , (. 4 5 ;

4 8, ;

5 1, ). ( . 4 9, ).

(3-4 %) , - , - (. 4 6 ;

55, ) - , . .

. 45. - ., 13 (- ). , - , (. 45). , (. 4 9, ).

- (. 4 7. 50) ) ) . 46. - ., 6 (- ). - : ) : ) ) ) 47. - ., 6 (- ):

) ;

) ) ) . 48. - - ., 6 (- ): ) - : ;

) - : ) 6) . 49. - ., 6 (- ):

) - : ;

) - : , , ( 50, 53) ) ) . 50. - ., 6 (- ):

) - , ;

) - (), ) ) . 51 - - ., 10 (- ):

) - : ;

) - : ) ) 52. - ., 10 (- ):

) ;

) ) ) . 53. - ., 10 (- ): ) - ;

) , - (, 5 4, ), - ( 5 4, ).

) 6) . 54. - .,15 (- ) ) ;

) - , (. 55 , ). , , .

(. 5 5, ).

. 55. - -: , ) ;

) ();

) 1.3.2. , , . , , , , , , .

, , (, , , , , 2 1 , , . ), / .

, , έ ( . 14) , FAB. I4.FAB / . , ( ), 2 0 % . t(8;

21), t ( 1 5 ;

1 7 ), inv (16), [14]. , [156,157].

, , ( ), , , [158].

, . , , , [ 1 5 9 ]. / [160].

therapyrelated

( ), , : 1) ;

2) II [ 1 4 ].

, FAB, , [ 1 4 ].

, , 10 50 % [ 1 6 1 1 6 4 ]. , , A M L B F M, ( ), A M L - B F M - 9 3, 50 6 1 % [ 1 6 5 ]. , .

(-0-3, 2000) [84] 984-993 (42.1) 9840/3 , 9860/3 , 9861/3 , 9866/3 , t(15;

17)(q22;

q11-12) 9867/3 9870/3 9871/3 9872/3 9873/3 9874/3 9891/3 9895/3 9896/3 , t(8;

21)(q22;

q22) 9897/3 , 11 q 9910/3 9920/3 ( ) , 9930/3 9931/3 (42.1) 9948/3 NK- :

, , . , , : ( ) ( ). , , 8 0 - 9 0 % [ 1 6 6 - 1 7 0 ]. [ 1 7 1 - 1 7 3 ], , .

. . - [166,168-170,174-177]. ( , ) () [ 1 7 8 - 1 8 0 ], . . , [181,182]. - , , .

, , , ( FLT3-ITDS [183]) . - , , . , , , , (-), [184-186].

. , , - [ 1 8 7 ].



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