Frequent CD7 Antigen Loss in Aggressive Natural Killer-Cell Leukemia: A Useful Diagnostic Marker

Eun-Hyung Yoo; Hee-Jin Kim; Seung-Tae Lee; Won-Seog Kim; Sun-Hee Kim

doi:10.3343/kjlm.2009.29.6.491

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Yoo, Kim, Lee, Kim, and Kim: Frequent CD7 Antigen Loss in Aggressive Natural Killer-Cell Leukemia: A Useful Diagnostic Marker

Original Article

Korean J Leg Med 2009;29(6):491-496.

Published online: 14 January 2009

DOI: https://doi.org/10.3343/kjlm.2009.29.6.491

Frequent CD7 Antigen Loss in Aggressive Natural Killer-Cell Leukemia: A Useful Diagnostic Marker

Eun-Hyung Yoo, M.D.¹, Hee-Jin Kim, M.D.¹, Seung-Tae Lee, M.D.¹, Won-Seog Kim, M.D.², Sun-Hee Kim, M.D.¹

¹Departments of Laboratory Medicine, Seoul, Korea

²Genetics and Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Corresponding author: Sun-Hee Kim, M.D. Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea Tel: +82-2-3410-2704, Fax: +82-2-3410-2719 E-mail: sunnyhk@skku.edu

Revised 2 January 20091 September 2009 Accepted 18 October 2009

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:

Aggressive natural killer-cell leukemia (ANKL) is a rare neoplasm characterized by systemic proliferation of NK cells. However, the differential diagnosis of NK lymphoproliferative disorders is difficult because of the absence of a distinct diagnostic hallmark. Therefore, to identify diagnostic markers for ANKL, we analyzed the clinical data and laboratory findings obtained for 20 patients with ANKL.

Methods:

From January 2000 to July 2007, 20 patients were diagnosed with ANKL on the basis of bone marrow studies. We retrospectively analyzed the clinical features and laboratory findings, including the complete blood count, Epstein-Barr virus status, immunophenotype, and the cytogenetic results.

Results:

The subjects included 6 women and 14 men (median age, 44 yr; range, 2-70 yr). Cytogenetic studies were performed in 18 patients, and karyotypic abnormalities were observed in 9 patients (50%). None of the cytogenetic abnormalities were constantly observed in all the patients. However, 6q abnormalities were observed in 4 patients (4/18, 22%). The immunophenotype of the leukemic NK-cells was cytoplasmic CD3⁺, surface CD3^-, CD16/56⁺, CD2⁺, and CD5^-. Notably, the CD7 antigen was absent in 10 patients (50%). When the CD7 loss was combined with cytogenetic abnormalities, clonal markers could be identified in 75% of the ANKL cases.

Conclusions:

The CD7 antigen loss was frequently observed in our series of ANKL patients. In conjunction with the cytogenetic findings, this characteristic immunophenotypic finding can serve as a reliable marker for the timely diagnosis of ANKL. Therefore, immunophenotypic analysis of CD7 expression should be included in the diagnosis of NK cell neoplasms.

Keywords: Aggressive natural killer cell leukemia (ANKL), Clonal marker, Immunophenotype, CD7, Cytogenetics

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Table 1.

The clinical and laboratory characteristics of 20 patients with aggressive natural killer-cell leukemia

Case no	Sex	Age (yr)	Hb (g/dL)	WBC (/μL)	PLT (×10³/μL)	BM/PB LGL morphology (%)	Survival time (months)	sCD3	cCD3	CD4	CD7	CD8	CD16/56	EBV status	Cytogenetic study results
1	F	50	8.6	6,100	100	64.1/1	2	-	+	-	+	-	+	+	45,X,-X,i(7)(q10),i(17)(q10),add(19)(p13)[5]/44,idem,-18[3]/45,idem,add(11)(p15)[2]/44,idem,add(3)(p26),-18[1]/44,idem,add(5)(p15.3),18[1]/ 46,XX[8]
2	F	14	6.8	5,700	36	8.4/1	1	-	+	-	+	-	+	NT	47,XX,+del(X)(q13),der(11)t(1;11)(q21;q25)[10]/46,XX[10]
3	M	37	10.3	3,200	79	3.9/0	4	-	+	+	-	NT	+	+	NT
4	F	62	9.1	900	44	12/0	1	-	+	-	+	-	+	+	79-85<4n>,XXXX,-X,add(6)(q23),add(7)(q36),-8,del(8)(p21),-9,add(9)(p24),-10,der(10;13)(q10;q10),-12,add(12)(p13),+13, der(13;13)(q10;q10),der(13;17)(q10;q10),-18,der(18)t(1;18)(q21;p11.2),+20, −21,+22[cp8]/46,XX[12]
5	M	27	10.9	3,200	43	35/25	2	-	+	-	-	-	+	+	46,XY[13]
6	M	42	9.5	8,700	250	70/15	0.1	-	+	-	-	-	+	+	NT
7	F	20	9.6	2,620	91	3.8/1	96∗	-	+	+	-	+	+	+	46,XX[20]
8	M	21	8.6	26,440	44	22.2/10	3	-	+	NT	+	NT	+	+	46,X,-Y,dup(1)(?q12q42),+8[15]/46,XY[5]
9	M	2	8.4	5,150	35	9.8/1	0.17	-	+	NT	+	NT	+	NT	92,XXYY[2]/46,XY[18]
10	M	21	11.3	790	11	23.6/0	12	-	-	+	-	NT	+	-	47,XY,der(6)del(6)(p21.3)del(6)(q23q25),add(11)(p11.2),der(16;19)(q10;p10),der(22)t(16;22)(p11.2;q13),+2mar[1]/48,idem.+r[2]/46,XY[4]
11	M	48	9.7	1,260	112	2.6/1	F/U loss	-	+	NT	-	-	+	-	46,XY[20]
12	M	45	10.8	1,490	76	29.4/4	9	-	+	-	-	NT	+	+	46,XY[2]
13	F	48	7.7	15,950	18	37.5/7	1.6	-	+	-	-	-	+	+	88,XX,-X,-X,add(4)(q34),del(4)(q22),del(6)(q21)x2,i(7)(q10)x2,+8,+8,-11,del(11)(q12),der(13)t(5;13)(q12;p13),i(13)(q10),-14,-18,-18[cp16]/46,XX[4]
14	M	45	8.7	5,000	32	20.8/30	1	-	+	-	+	-	+	+	46,XY[8]
15	M	36	8.1	380	24	21.8/0	0.23	-	+	-	+	-	+	+	46,XY[20]
16	M	48	8.2	1,570	28	8/0	3	-	+	-	+	+	+	+	46,XY[20]
17	F	45	7.9	1,050	48	18.2/0	0.6	-	+	-	-	-	+	+	46,XX,add(3)(q26),+9,der(9;14)(p10;q10)[2]/46,XX[19]
18	M	70	9	700	37	13.2/0	1.6	-	+	-	-	+	+	+	47,XY,+X,+1,der(1;16)(q10;p10),add(3)(p23),del(6)(q21),add(9)(p2?2),del(14)(q24),+16,-22[5]/46,XY[7]
19	M	16	10.5	5,500	104	8.6/7	11	-	+	-	+	-	+	-	46,XY[20]
20	M	60	17	18,800	47	12.4/0	0.27	-	+	NT	+	NT	+	+	46,XY[20]
	M:F	44 (2-	9.1	3,200	44	16/1	1.3	0/20	19/20	3/16	10/20	3/14	20/20	15/18
	14:6	70)	(6.8-17.0)	(380-26,440)	(11-250)	(3-70)/(0-30)		(0%)	(95%)	(19%)	(50%)	(21%)	(100%)	(83.3%)

^∗ Alive, autologous peripheral stem cell transplantation was performed twice.

Abbreviations: WBC, white blood cells; PLT, platelets; BM, bone marrow; LGL, large granular lymphocytes; NT, not tested; M:F, male-to-female ratio.

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