Brief Communication Acta Haematol 2014;132:244–246 DOI: 10.1159/000358188
Received: December 9, 2013 Accepted: December 20, 2013 Published online: May 22, 2014
Unbalanced Translocation der(7)t(7q;11q): A New Recurrent Aberration Leading to Partial Monosomy 7q and Trisomy 11q in Acute Myeloid Leukemia Katsuya Yamamoto Kimikazu Yakushijin Yoshiharu Miyata Hiroshi Matsuoka Hironobu Minami Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
Unbalanced translocations, which are created if one of the two derivative chromosomes is lost, often result in the loss or gain of chromosomal material rather than the formation of fusion genes in hematological malignancies [1]. They are usually part of complex karyotypes, diagnostically nonspecific and related to disease progression, although some of them seem to be a recurrent and primary anomaly [2, 3]. Recently, unbalanced translocations involving chromosome 11, such as der(18)t(11; 18) (q13;q21.1) and der(7)t(7; 11)(q31;q14), have been reported in acute myeloid leukemia (AML) [4, 5]. These translocations occurred as a sole abnormality at diagnosis, and resulted in partial trisomy 11q including three copies of the MLL gene at 11q23. Here, we describe a new case of AML with der(7)t(7q;11q), which led to partial monosomy 7q and partial trisomy 11q including MLL. A 79-year-old Vietnamese male was admitted because of anemia. He had no history of chemoradiotherapy. Peripheral blood showed Hb 7.0 g/dl, PLT 44 × 109/l and WBC 18.5 × 109/l with 25% myeloblasts, 6% myelocytes, 16% metamyelocytes, 5% band forms, 24% segmented neutrophils, 1% basophils, 12% monocytes and 11% lymphocytes. Bone marrow was hypercellular with 22.1% myeloblasts, 66.2% myeloid cells and 0.8% erythroblasts. Blasts were positive for myeloperoxidase staining and im© 2014 S. Karger AG, Basel 0001–5792/14/1322–0244$39.50/0 E-Mail [email protected] www.karger.com/aha
munophenotypically positive for CD13, CD33, CD34 and HLA-DR. Considering dysplastic changes of bone marrow cells, we made a diagnosis of AML with myelodysplasia-related changes (MRC). The patient received an induction therapy with aclarubicin and low-dose cytarabine followed by six courses of azacitidine therapy, but he could not achieve complete remission. He died of progressive disease 10 months after the initial diagnosis. G-banding and spectral karyotyping of bone marrow cells at diagnosis showed 46,XY,der(7)t(7;11)(q11.2;q13) [18]/46,sl,add(3)(p11)[2] (fig. 1a, b). The karyotype after 6 months was also 46,XY,der(7)t(7; 11)(q11.2;q13)[20]. Fluorescence in situ hybridization (FISH) on metaphase spreads detected three MLL signals on the der(7)t(7;11) and two normal chromosomes 11 (fig. 1c), whereas one D7S486 signal at 7q31 was deleted from the der(7)t(7;11) (fig. 1d). These findings confirmed that the der(7)t(7;11) (q11.2;q13) as a sole abnormality resulted in partial monosomy 7q and partial trisomy 11q including MLL amplification without rearrangement [5, 6]. In addition, we examined the possible involvement of RUNX1 at 21q22 by FISH on interphase nuclei, because De Braekeleer et al. [5] revealed an abnormal clone with a cryptic RUNX1 deletion, which was distinct from the clone with der(7)t(7; 11)(q31;q14), in AML at diagnosis. However, Katsuya Yamamoto Division of Medical Oncology/Hematology Department of Medicine, Kobe University Graduate School of Medicine 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan) E-Mail kyamamo @ med.kobe-u.ac.jp
7
a
11
b
3
6
7
8
13
14
15
19
9
20
1
10
4
5
11
12
16
21
17
22
Color version available online
2
1
18
X
Y
2
e
1 2
1
c
d
Fig. 1. a Partial G-banded karyotype of bone marrow cells at the initial diagnosis. Only chromosomes 7 and 11 are shown. The arrow indicates the rearranged chromosome. b Spectral karyotyping of the metaphase spreads after spectrum-based classification (left side: reverse DAPI and right side: SKY). The karyotype is 46,XY,der(7)t(7; 11)(q11.2;q13). The arrow indicates the rearranged chromosome. c FISH with Vysis LSI MLL Dual Color, Break Apart Rearrangement Probe (Abbott Molecular, Abbott Park, Ill., USA) on metaphase spreads. Arrows indicate MLL signals (green/red, yellow) at 11q23 on (1) two normal chromosomes 11 and (2) der(7)t(7; 11)(q11.2;q13). d FISH with Vysis D7S486/ CEP 7 FISH Probe Kit (Abbott Molecular) on metaphase spreads.
f
Arrows indicate (1) D7S486 signal (red) at 7q31 and CEP 7 signal (green) at 7p11.1-q11.1 on a normal chromosome 7 and (2) CEP 7 signal on the der(7)t(7;11)(q11.2;q13). e, f FISH with the combination of LSI MLL Dual Color, Break Apart Rearrangement Probe and Vysis LSI ETV6 (TEL)/RUNX1 (AML1) ES Dual Color Translocation Probe Set (Abbott Molecular) on interphase nuclei. Arrows indicate MLL signals. e Three MLL (yellow), two ETV6 (green) and two RUNX1 (red) signals are found in one cell with der(7)t(7;11)(q11.2;q13). f Two MLL, two ETV6 and two RUNX1 signals are observed in one cell without der(7)t(7; 11). That is, RUNX1 deletion could not be detected in both clones. Colors refer to the online version only.
Table 1. Reported cases of hematological malignancies with der(7)t(7q;11q) as a sole abnormality Case Age/ No. sex
Diagnosis
Karyotypes
MLL WBC, Hb, copy ×109/l g/dl (blast %)
1
7/F
t-AML
46,XX,der(7)t(7;11)(q22;q14)[20]
3
34.5 (78) 11.0
AML-MRC 46,XX,der(7)t(7;11)(q11;q13)[8]/46,XX[2]
3
n.a.
2
82/F
3
51/M AML M1
4
79/M AML-MRC 46,XY,der(7)t(7;11)(q11.2;q13)[18]/46,sl, add(3)(p11)[2]
46,XY,der(7)t(7;11)(q31;q14)[7]/46,XY[15]
3 3
PLT, BM Immunophenotypes ×109/l blast, % 62
n.a.
OS, Ref. months
CD7, CD3, CD2, CD13, 12 CD15, CD34, HLA-DR, CD117
[6]
n.a.
n.a.
n.a.
n.a.
Received: December 9, 2013 Accepted: December 20, 2013 Published online: May 22, 2014
Unbalanced Translocation der(7)t(7q;11q): A New Recurrent Aberration Leading to Partial Monosomy 7q and Trisomy 11q in Acute Myeloid Leukemia Katsuya Yamamoto Kimikazu Yakushijin Yoshiharu Miyata Hiroshi Matsuoka Hironobu Minami Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
Unbalanced translocations, which are created if one of the two derivative chromosomes is lost, often result in the loss or gain of chromosomal material rather than the formation of fusion genes in hematological malignancies [1]. They are usually part of complex karyotypes, diagnostically nonspecific and related to disease progression, although some of them seem to be a recurrent and primary anomaly [2, 3]. Recently, unbalanced translocations involving chromosome 11, such as der(18)t(11; 18) (q13;q21.1) and der(7)t(7; 11)(q31;q14), have been reported in acute myeloid leukemia (AML) [4, 5]. These translocations occurred as a sole abnormality at diagnosis, and resulted in partial trisomy 11q including three copies of the MLL gene at 11q23. Here, we describe a new case of AML with der(7)t(7q;11q), which led to partial monosomy 7q and partial trisomy 11q including MLL. A 79-year-old Vietnamese male was admitted because of anemia. He had no history of chemoradiotherapy. Peripheral blood showed Hb 7.0 g/dl, PLT 44 × 109/l and WBC 18.5 × 109/l with 25% myeloblasts, 6% myelocytes, 16% metamyelocytes, 5% band forms, 24% segmented neutrophils, 1% basophils, 12% monocytes and 11% lymphocytes. Bone marrow was hypercellular with 22.1% myeloblasts, 66.2% myeloid cells and 0.8% erythroblasts. Blasts were positive for myeloperoxidase staining and im© 2014 S. Karger AG, Basel 0001–5792/14/1322–0244$39.50/0 E-Mail [email protected] www.karger.com/aha
munophenotypically positive for CD13, CD33, CD34 and HLA-DR. Considering dysplastic changes of bone marrow cells, we made a diagnosis of AML with myelodysplasia-related changes (MRC). The patient received an induction therapy with aclarubicin and low-dose cytarabine followed by six courses of azacitidine therapy, but he could not achieve complete remission. He died of progressive disease 10 months after the initial diagnosis. G-banding and spectral karyotyping of bone marrow cells at diagnosis showed 46,XY,der(7)t(7;11)(q11.2;q13) [18]/46,sl,add(3)(p11)[2] (fig. 1a, b). The karyotype after 6 months was also 46,XY,der(7)t(7; 11)(q11.2;q13)[20]. Fluorescence in situ hybridization (FISH) on metaphase spreads detected three MLL signals on the der(7)t(7;11) and two normal chromosomes 11 (fig. 1c), whereas one D7S486 signal at 7q31 was deleted from the der(7)t(7;11) (fig. 1d). These findings confirmed that the der(7)t(7;11) (q11.2;q13) as a sole abnormality resulted in partial monosomy 7q and partial trisomy 11q including MLL amplification without rearrangement [5, 6]. In addition, we examined the possible involvement of RUNX1 at 21q22 by FISH on interphase nuclei, because De Braekeleer et al. [5] revealed an abnormal clone with a cryptic RUNX1 deletion, which was distinct from the clone with der(7)t(7; 11)(q31;q14), in AML at diagnosis. However, Katsuya Yamamoto Division of Medical Oncology/Hematology Department of Medicine, Kobe University Graduate School of Medicine 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan) E-Mail kyamamo @ med.kobe-u.ac.jp
7
a
11
b
3
6
7
8
13
14
15
19
9
20
1
10
4
5
11
12
16
21
17
22
Color version available online
2
1
18
X
Y
2
e
1 2
1
c
d
Fig. 1. a Partial G-banded karyotype of bone marrow cells at the initial diagnosis. Only chromosomes 7 and 11 are shown. The arrow indicates the rearranged chromosome. b Spectral karyotyping of the metaphase spreads after spectrum-based classification (left side: reverse DAPI and right side: SKY). The karyotype is 46,XY,der(7)t(7; 11)(q11.2;q13). The arrow indicates the rearranged chromosome. c FISH with Vysis LSI MLL Dual Color, Break Apart Rearrangement Probe (Abbott Molecular, Abbott Park, Ill., USA) on metaphase spreads. Arrows indicate MLL signals (green/red, yellow) at 11q23 on (1) two normal chromosomes 11 and (2) der(7)t(7; 11)(q11.2;q13). d FISH with Vysis D7S486/ CEP 7 FISH Probe Kit (Abbott Molecular) on metaphase spreads.
f
Arrows indicate (1) D7S486 signal (red) at 7q31 and CEP 7 signal (green) at 7p11.1-q11.1 on a normal chromosome 7 and (2) CEP 7 signal on the der(7)t(7;11)(q11.2;q13). e, f FISH with the combination of LSI MLL Dual Color, Break Apart Rearrangement Probe and Vysis LSI ETV6 (TEL)/RUNX1 (AML1) ES Dual Color Translocation Probe Set (Abbott Molecular) on interphase nuclei. Arrows indicate MLL signals. e Three MLL (yellow), two ETV6 (green) and two RUNX1 (red) signals are found in one cell with der(7)t(7;11)(q11.2;q13). f Two MLL, two ETV6 and two RUNX1 signals are observed in one cell without der(7)t(7; 11). That is, RUNX1 deletion could not be detected in both clones. Colors refer to the online version only.
Table 1. Reported cases of hematological malignancies with der(7)t(7q;11q) as a sole abnormality Case Age/ No. sex
Diagnosis
Karyotypes
MLL WBC, Hb, copy ×109/l g/dl (blast %)
1
7/F
t-AML
46,XX,der(7)t(7;11)(q22;q14)[20]
3
34.5 (78) 11.0
AML-MRC 46,XX,der(7)t(7;11)(q11;q13)[8]/46,XX[2]
3
n.a.
2
82/F
3
51/M AML M1
4
79/M AML-MRC 46,XY,der(7)t(7;11)(q11.2;q13)[18]/46,sl, add(3)(p11)[2]
46,XY,der(7)t(7;11)(q31;q14)[7]/46,XY[15]
3 3
PLT, BM Immunophenotypes ×109/l blast, % 62
n.a.
OS, Ref. months
CD7, CD3, CD2, CD13, 12 CD15, CD34, HLA-DR, CD117
[6]
n.a.
n.a.
n.a.
n.a.
