kjlm The Korean Journal of Laboratory Medicine Korean J Lab Med 2383-5702 2383-5710 The Korean Society for Laboratory Medicine 10.3343/kjlm.2007.27.4.237 kjlm-27-237 Original Article Prevalence of FLT3 Internal Tandem Duplication in Adult Acute Myelogenous Leukemia LeeJeong NyeoM.D. 1 3 KimHye RanM.D. 1 ShinJeong HwanM.D. 1 3 JooYoung DonM.D. 2 Department of Laboratory Medicine, Busan Paik Hospital, College of Medicine, Inje University, Busan, Korea Department of Internal Medine, Busan Paik Hospital, College of Medicine, Inje University, Busan, Korea Department of Internal Medine, Institute for Clinical Research, Inje University, Busan, Korea 022007 10022007 27 4 237 243 14092006 03052007 19062007 Copyright © 2007 The Korean Society for Laboratory Medicine 2007 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background

fms-like tyrosine kinase (FLT3), a member of the class III receptor tyrosine kinases, regulates the proliferation and differentiation of hematopoietic stem cells. An internal tandem duplication of the FLT3 gene (FLT3/ITD) has been reported in acute myelogenous leukemia (AML) and may be associated with a poor prognosis. In this study we determined the prevalence and prognostic significance of FLT3/ITD in adult AML patients.

 Methods

This study included 52 adult de novo AML. Exon 14 and 15 of the FLT3 gene were amplified by PCR and the PCR products were analyzed by 3730XL DNA analyzer (Applied Biosystems, USA) and GeneMapper Software.

 Results

FLT3/ITD was found in 15 (28.8%) of the 52 AML patients. The presence of FLT3/ITD was significantly associated with absolute leukocyte counts (P=0.002) and bone marrow blast counts (P=0.036). FLT3/ITD was also more frequent in patients with normal karyotype (7 of 18) than in those with cytogenetic aberrations (3 of 25). Patients with t (15;17) showed a higher prevalence of FLT3/ITD (2 of 7). FLT3/ITD was significantly associated with overall survival (P<0.042).

 Conclusions

Our data indicate that FLT3/ITD is a common alteration in adult AML patients. Although based on a study with a limited number of AML patients, FLT3/ITD is a prognostic marker in patients with AML.

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Gene scan analysis of FLT3/ITD in patients with ITD of different size. (A) wild type of FLT3 gene, (B-D) wild type and various size of ITD in FLT3 gene.

Abbrevications: FLT3, fms-like tyrosine kinase; ITD, internal tandem duplication.

Kaplan-Meier plot of the overall survival of patients with acute myelogenous leukemia according to FLT3 mutations.

Abbrevications: See Fig. 1.

Clinical characteristics according to the FLT3 status in patients with de novo AML

  Total patients FLT3 positive patients FLT3 negative patients
N of cases (%) 52 15 (28.8%) 37 (71.2%)
Age, yr, median (range) 50 (20–80) 53 (20–80) 49 (22–79)
Male/Female ratio 25:27 6:9* 19:18
WBC count×109/L, median (range) 14.1 (0.7–145) 63.2 (2.7–145)* 12.9 (0.7–125)
Platelet count×1012/L, median (range) 40 (1.5–246) 48 (12–246) 33 (1.5–150)
Bone marrow blasts, % (range) 72 (31–95) 87 (35–92)† 69 (31–95)
FAB classification      
M0 2 0 2
M1 17 6 11
M2 18 3 15
M3 11 5 6
M5 2 1 1
M6 1 0 1
M7 1 0 1
Cytogenetic results      
Normal 18 7 11
t(8;21) 7 0 7
t(15;17) 7 2 5
t(3;3) 1 0 1
t(7;11) 1 1 0
t(1:19) 1 0 1
+8/+10/+11 4 0 4
Multiple aberrations 4 0 4
N/A* 9 5 4

N/A; 5 patients had no mitotic cells in culture and cytogenetic analysis could not be performed on four patients.

P<0.01;

P<0.05.

Abbrevications: FLT3, fms-like tyrosine kinase; AML, acute myelogenous leukemia.

Cytogenetic and gene scan analysis in patients with FLT3/ITD

No. Age/Sex WBC (×109/L) Platelet (×109/L) Blast (%) FAB Allele FLT3 ratio wild/mutant Chromosome
1 44/F 123.8 41 86 M1 329–356 0.52 46,XX,t(7;11)(p15;p15)[20]
2 51/M 7.8 30 63 M1 329–382 0.44 46,XY[20]
3 20/F 133.8 60 83 M1 329–382 0.99 46,XX[20]
4 53/F 2.7 86 92 M1 329–350 0.59 46,XX
5 66/M 53.0 84 89 M1 329–396 0.42 46,XY[7]
6 58/M 7.5 36 89 M1 329–390 0.33 No Test
7 47/M 72.2 48 92 M2 329–353–382 0.90 No mitotic cell
8 80/F 145.0 151 86 M2 329–376 0.35 No mitotic cell
9 67/M 11.5 246 61 M2 329–402 0.16 46,XY
10 39/F 43.7 20 88 M3 329–350 0.33 46,XX
11 43/F 7.9 15 87 M3 329–350 0.45 46,XX,t(15;17)(q22;q12)[15]
12 66/F 86.5 33 43 M3 329–382 0.35 No test
13 70/F 101.9 112 83 M3 329–353–359 0.45 No test
14 55/F 95.3 23 91 M3 329–379–396 0.48 46,XX,t(15;17)(q22;q12)[20]
15 37/M 63.2 205 35 M5b 329–379 0.25 46,XY[20]

Abbrevications: See Fig. 1.