Prevalence of FLT3 Internal Tandem Duplication in Adult Acute Myelogenous Leukemia

Jeong Nyeo Lee; Hye Ran Kim; Jeong Hwan Shin; Young Don Joo

doi:10.3343/kjlm.2007.27.4.237

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Lee, Kim, Shin, and Joo: Prevalence of FLT3 Internal Tandem Duplication in Adult Acute Myelogenous Leukemia

Original Article

Korean J Leg Med 2007;27(4):237-243.

Published online: 10 February 2007

DOI: https://doi.org/10.3343/kjlm.2007.27.4.237

Prevalence of FLT3 Internal Tandem Duplication in Adult Acute Myelogenous Leukemia

Jeong Nyeo Lee, M.D.^1,³, Hye Ran Kim, M.D.¹, Jeong Hwan Shin, M.D.^1,³, Young Don Joo, M.D.²

¹Department of Laboratory Medicine, Busan Paik Hospital, College of Medicine, Inje University, Busan, Korea

²Department of Internal Medine, Busan Paik Hospital, College of Medicine, Inje University, Busan, Korea

³Department of Internal Medine, Institute for Clinical Research, Inje University, Busan, Korea

Received 14 September 2006 Revised 3 May 2007 Accepted 19 June 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.

Keywords: Adult, Acute myelogenous leukemia, FLT3/ITD

References

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Fig. 1.

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.

Fig. 2.

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

Abbrevications: See Fig. 1.

Table 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.

Table 2.

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.

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