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der(15)t(1;15)(q11-12;p11-13) and der(15)t(1;15)(q21-25;p10-13)

Written2017-11Adriana Zamecnikova
Kuwait Cancer Control Center, Kuwait

Abstract Unbalanced 1q translocations leading to complete or partial trisomies of the long arm of chromosome 1 have been widely reported in both lymphoid and myeloid neoplasms. Chromosomal translocations between the long arm of chromosome 1 and the acrocentric chromosome 15 are mostly secondary events representing clonal evolution.

Keywords Gain of 1q, unbalanced translocations, acrocentric chromosomes, gene overexpression.

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ICD-Topo C420,C421,C424
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9671/3 Lymphoplasmacytic lymphoma
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9687/3 Burkitt lymphoma
ICD-Morpho 9827/3 Adult T-cell leukaemia/lymphoma
ICD-Morpho 9673/3 Mantle cell lymphoma
ICD-Morpho 9680/3 Diffuse large B-cell lymphoma (DLBCL), NOS; Primary DLBCL of the CNS; Primary cutaneous DLBCL, leg type; EBV positive DLBCL of the elderly; DLBCL associated with chronic inflammation; B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma
ICD-Morpho 9690/3 Follicular lymphoma; Paediatric follicular lymphoma
ICD-Morpho 9732/3 Plasma cell myeloma / Multiple myeloma
Atlas_Id 1811
  Figure 1. Partial karyotypes with der(15)t(1;15)(q11;p11-13).
  Figure 2. Fluorescence in situ hybridization with LSI 1p36/1q25 probe (Vysis, Abott Molecular, US) showing the extra green signal of 1q25 on der(15) chromosome (A). Hybridization with LSI PML/RARA probe revealing the red signal for PML located on der(15) chromosome (B).

Clinics and Pathology

Disease Chronic and acute myeloid malignancies, B-cell acute lymphoblastic leukemia (ALL), multiple myeloma (MM) and lymphomas.
Phenotype / cell stem origin
Etiology Patients with der(15)t(1;15)(q11;p11-13) were diagnosed mainly with myeloid malignancies (10 patients): 1 polycythemia vera (PV) (Sanford et al., 2015), 5 myelodysplastic syndromes (MDS) (Mecucci et al., 1986; Mascarello et al., 1989; Jotterand-Bellomo et al., 1990; Najfeld et al., 1995) and 5 patients were diagnosed with acute myeloid leukemia (AML) (Andrieux et al., 2006; Farag et al., 2006; Poppe et al., 2006; Liu et al., 2007; Manola et al., 2008). In addition, there was 1 female with non neoplastic disorder (aplastic anemia) (Kim et al., 2010). Acute lymphoblastic leukemia was diagnosed in 7 (Raimondi et al., 1990; Heerema et al., 1999; Rafi et al., 2000; Boomer et al., 2001; Wan et al., 2004; Wetzler et al., 2004; Coyaud et al., 2010) and multiple myeloma in 3 (Calasanz et al., 1997; Rajkumar et al., 1999; Smadja et., al 2001). 7 patients has various B-cell lymphomas: 1 mature B-cell neoplasm (MBCL), 3 follicular lymphoma (FL) (Horsman et al., 2001; Le Baccon et al., 2001; Narayan et al., 2013), 2 diffuse large B-cell lymphoma (DLBL) (Fan & Rizkalla., 2003; Havelange et al., 2013) and 1 mantle cell lymphoma (MCL) (Fan & Rizkalla., 2003) (Table 1).
Patients with der(15)t(1;15)(q21-25;p10-13) were diagnosed with lymphoproliferative malignancies (10 patients), among them acute lymphoblastic leukemia in 3 (Strefford et al., 2007; Schmiegelow et al., 2012; Safavi et al., 2015) and various, mainly B-cell lymphomas in 9: 1 adult T-cell lymphoma/leukemia (HTLV-1+) (ATLL) (Kamada et al., 1992), 4 diffuse large B-cell lymphomas (DLBCL) (Sandlund et al., 1994; Miura et al., 1996; Aamot et al., 2005; Zhang et al., 2009), 1 lymphoplasmacytic lymphoma (LPL) (Khokhar et al., 1995), 1 Burkitt lymphoma/leukemia (BL) (Silva et al., 2002) and 2 follicular lymphomas (FL) (Lestou et al., 2003; Keller et al., 2006). Sporadic cases of other malignancies: 1 acute myeloid leukemia (AML) (Olsson et al., 2016) and 1 multiple myeloma (MM) (Nakano et al., 2005).
Table 1. Clinical and karyotypic data of patients with der(15)t(1;15)(q11-12;p11-13).
 Sex/ AgeDiseaseKaryotype
8F/65AML-M546,XX,add(6)(p12),der(12)t(12;?19)(p13;?p12) or der(12)t(12;?19)(p13;q12),del(13)(q21q31),der(15)t(1;15) (q11-12;p12),add(21)(q22)/46,idem,-16,+mar
12F/28AML-M146,XX,+1,der(1;7)(q10;p10)/46,XX,+1,dic(1;11)(p11;q25)/46,XX,t(1;6)(p32;q25-27),der(7)t(7;12)(q11-22;q13-15), der(12)t(1;12)(q11-12;q13-15)/46,XX,der(15)t(1;15)(q11;p11)s
13M B- ALL49,XY,+Y,-6,+10,der(12)t(6;12)(q21;p13),der(19)t(1;19)(q23;p13),+21,+21/49,XY,+Y,+7,der(15)t(1;15)(q11;p11), der(19),+21/50,XY,+7,+17,der(19),+20,+21
15M/13B-ALL45,XY,add(3)(q27),del(8)(p22),t(8;22)(q24;q11),add(9)(p24),-10,t(12;21)(p13;q22),der(15)t(1;15)(q11;p11), der(22) t(1;22)(q11;p11)
22FMM44,XX,-1,der(8)t(1;8)(p11-12;q24),t(11;14)(q13;q32),del(14)(q21q32),der(15)t(1;15)(q12;p11),add(16)(q10),der(18) t(11;18)(q13;p11)ins(18;?1)(p11;?)ins(18;14)(p11;q32q32),-22,+mar
23F/65 MBCL49,X,t(X;1)(p2?1;p3?1),+5,del(9)(q12q22),t(11;18;11)(p15;q21;q23),+13,del(13)(q12q14)x2,add(14)(q32), der(15) t(1;15)(q11;p11),+der(18)t(11;18)(p15;q21)/48,X,t(X;1),+11,del(13),add(14),der(15),+mar  LN
24F/57 FL  46,XX,t(14;18)(q32;q21),der(15)t(1;15)(q11;p11) LN
25F/81 FL 44,XX,+X,t(1;2)(q25;q37),dic(9;?22)(q21;p11),add(10)(p15),add(11)(p13),del(12)(?q14?q24),-13,del(14)(q24q32),der(14)add(14)(p11)t(14;18)(q32;q21),-15,der(15)t(1;15)(q12;p11),-16,-17,-18,del(20)(q11),-21,+3mar LN
26MMCL 43-44,XY,del(1)(p12p31),der(1)t(1;21)(p11;q11),der(10)t(10;22)(p13;q11),der(11)t(11;14)(q13;q32),der(14)t(11;14) del(11)(q23),der(15)t(1;15)(q12;p11),-21,-2 LN
27FDLBL 45,X,-X,der(2)t(2;3)(q31;p?),del(3)(p13p23),-4,del(6)(q13),+7,del(10)(q25),ins(10;9)(q11;q13q22) or ins(10;9) (q11;q22q34),del(13)(q12q14),der(14)t(3;14)(p?;p11),t(14;18)(q32;q21),der(15)t(1;15)(q12;p11),der(16)t(16;17) (q12;q21) LN
28F/14 DLBCL46,X,-X,der(X)t(X;4)(p21;q21),der(X)t(X;10;4)(p21;?;q12),der(3)t(3;18)(q11;q21),dup(3)(q13q24),del(4)(q12), der(4)t(X;4)(?;p16),t(8;22)(q24;q11),der(9)t(3;9)(p13;p21),t(9;20)(q10;p10),der(10)t(3;10)(?;q11),dup(11)(q23q13),der(11)dup(11)(q23q13)t(1;11)(?;q25),der(11)dup(11)(q23q13)t(3;11)(?;q25),der(11)dup(11)(q23q13)t(7;11)(?;q25),dup(11)(q23q13),trp(13)(q22q32),der(14)t(X;14)(q13;q24),der(15)t(1;15)(q11;p11),der(16)t(1;16)(p2?;q1?),der(17)t(X;17)(q21;p11),der(17)t(X;17;6)(p11;p11q25;?),der(18)t(4;18)(?;q23),der(18)t(6;18)(?;q23),dup(18)(q11q23),der(22)t(16;22)(?;q1?3) exudate
29F/65 FL90-96,XXXX,+X,+X,ins(1;?)(q21;?)x2,add(1)(p22),del(3)(q11),i(3)(p10),-4,der(15)t(1;15)(q11;p11)x2,i(17)(q10) x2,+21,+21,+1-6mar LN

Abbreviations: M, male; F, female; AA, Aplastic anemia, RARS, Refractory anemia with ringed sideroblasts; RA, Refractory anemia; RAEB, Refractory anemia with excess of blasts; PV, Polycythemia vera; AML-M5, Acute monoblastic leukemia with differentiation; AML, Acute myeloid leukemia; AML-M2, Acute myeloblastic leukemia with maturation; AML-M1, Acute myeloblastic leukemia without maturation; ALL,  Acute lymphoblastic leukemia; MM, Multiple myeloma; MBCN, Mature B-cell neoplasm; LN, lymph node, FL,  Follicular lymphoma, MCL, Mantle cell lymphoma; DLBCL, Diffuse large B-cell lymphoma.
1. Kim et al., 2010; 2-3. Mecucci et al., 1986; 4. Mascarello et al., 1989; 5. Jotterand-Bellomo et al., 1990; 6. Najfeld et al., 1995; 7. Sanford et al., 2015 ; 8. Andrieux et al., 2006; 9. Farag et al., 2006; 10. Poppe et al., 2006; 11. Liu et al., 2007; 12. Manola et al., 2008; 13. Raimondi et al., 1990; 14. Heerema et al., 1999; 15. Rafi et al., 2000; 16. Boomer et al., 2001; 17. Wan et al., 2004; 18. Wetzler et al., 2004; 19. Coyaud et al., 2010; 20. Calasanz et al., 1997; 21. Rajkumar et al., 1999; 22. Smadja et al., 2001; 23. Kobayashi et al., 1993; 24. Horsman et al., 2001; 25. Le Baccon et al., 2001; 26-27. Fan & Rizkalla 2003; 28. Havelange et al., 2013; 29. Narayan et al., 2013.
Table 2. Clinical and karyotypic data of patients with der(15)t(1;15)(q21-25;p10-13).
1M/11 AML46,XY,add(4)(p16),der(15)t(1;15)(q25;p12)/46,idem,del(5)(q22),der(8)t(5;8)(q31;q22)
3M/9 B-ALL46,XY,t(1;19)(q23;p13),der(14)t(1;14)(q21;p1?2),der(15)t(1;15)(q21;p1?2),der(22)t(1;22)(q21;p1?2)
4F/22 B-ALL46,XX,der(19)t(1;19)(q23;p13)/46,idem,der(15)t(1;15)(q21;p11)
5F/69 MM46,XX,der(15)t(1;15)(q21;p13)
6F/ 62 ATCL (HTLV-1+) 47,X,-X,add(1)(p12),add(3)(p25),+add(3)(q21),der(11)t(1;11)(p12;q14),add(14)(p11),der(15)t(1;15)(q21;p11),der(16)t(11;16)(q14;q13),-18,-22,+3mar
7M/10 DLBCL88-93,XYY,add(X)(q2?6),der(2)add(2)(p23)add(2)(q23),t(2;5)(p23;q35),add(3)(q29),add(3)(q27),add(4) (q22),del(6)(q21q23)x2,add(9)(p24),add(11)(q23)x2,der(15)t(1;15)(q21;p13),der(15)t(1;15)(q21;p13)t(1;1)(q42;q32),add(17)(p13),+mar,inc
8M/49 LPL  LN46,XY,t(1;4)(q21;q32),der(3)t(3;3)(p25;q21)dup(3)(q21q29),t(12;14)(q13;q32),der(14)t(1;14)(q21;q32),der(15)t(1;15)(q21;p12)
9M/62 DLBCL45,X,-Y,t(3;6)(q27;p21),der(6)t(6;8)(q27;q22),der(15)t(1;15)(q21;p13),del(16)(q22)
10F/11 BL46,XX,t(8;14)(q24;q32),der(15)t(1;15)(q21;p13)
11F/ FL LN47-49,XX,+7,+der(9)del(9)(p13)t(4;9)(?p14;q33),dup(12)(q13q22)x2,+14,der(15)t(1;15)(q23;p11),t(18;22)(q21;q11),+21,+der(21),+der(22),+der(22)t(3;22)(?q27;q11)
12MDLBCL LN52,XY,+Y,+der(3)t(3;9)(p11;p21)del(3)(q21),+7,+9,der(9)t(3;9)(q21;p21)x2,t(14;22)(q32;q11),der(15) t(1;5)(q21;p11),del(16)(p13),i(17)(q10),+18,+mar>
13M/79 FL  LN48,XY,+X,del(1)(p13),add(2)(p25),inv(3)(p24q27),t(8;14)(q24;q32),dup(12)(q12q24),t(14;18)(q32;q21),   -15,der(15)t(1;15)(q21;p10),add(16)(q24)
14M/32 DLBCL LN85-87,XXY,-1,i(1)(q10),-2,add(2)(p23),dic(3;7)(p23;q11),del(4)(q21),del(5)(q13),+der(5)t(3;5)(p13;q22), del(7)(q11),-9,add(9)(q34),t(9;14)(q13;q32),-10,-11,add(11)(p14),i(11)(q10),-12,der(13;13)(q10;q10),-14, -15,der(15)t(1;15)(q21;p13),-16,-16,-17,-17,-22,inc

Abbreviations: M, male; F, female; AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; MM, multiple myeloma;. ATLL, adult T-cell lymphoma/leukemia; DLBCL diffuse large B-cell lymphoma; LPL, lymphoplasmacytic lymphoma; LN, lymph node; BL, Burkitt lymphoma/leukemia; FL, follicular lymphoma.
1. Olsson et al., 2016; 2. Strefford et al., 2007; 3. Schmiegelow et al., 2012; 4. Safavi et al., 2015; 5. Nakano et al., 2005; 6. Kamada et al., 1992; 7. Sandlund et al., 1994; 8. Khokhar et al., 1995; 9. Miura et al., 1996; 10. Silva et al., 2002; 11. Lestou et al., 2003; 12. Aamot et al., 2005; 13. Keller et al., 2006; 14. Zhang et al., 2009.
Epidemiology The centromeric 1q11-12 translocation was reported at least in 29 patients (10 males and 19 females aged 0 to 81 years; median 47 years); among them there was 1 infant and 3 pediatric patients aged 13 to 15 years. Patients with 1q21-25 were less frequent and have been reported in 9 males and 5 females aged 6 to 79 years (median 22 years), 5 of them were children aged 6 to 11 years (4 males and 1 female).
Prognosis In patients with complex karyotypes the appearance of the abnormality is associated with advanced disease, therapy resistance and unfavorable prognosis.


Note To exclude the presence of dic(1;15)(p10-11;p10-11) or dic(1;15)(q10 11;q10-11) fluorescence in situ hybridization with centromere-specific probes for both chromosomes is recommended.
Cytogenetics Morphological der(15)t(1;15)(q11-2;p11-13) was found as a sole anomaly in 2 MDS (Mecucci et al., 1986; Jotterand-Bellomo et al., 1990), 1 AML (Farag et al., 2006) and in the aplastic anemia patient (Kim et al., 2010). Found in association with del(5)(q14q32) and del(20)(q11) in 1 MDS (Mecucci et al., 1986) and +8 and del(20)(q13) in PV (Sanford et al., 2015). Associated with der(19)t(1;19)(q23;p13)/t(1;19)(q23;p13) in 4 out of 7 ALL patients (Raimondi et al., 1990; Heerema et al., 1999; Boomer et al., 2001; Coyaud et al., 2010), t(9;22)(q34;q11) in 2 (Wan et al., 2004; Wetzler et al., 2004) and t(8;22)(q24;q11) in 1 (Rafi et al 2000). Found with t(11;14)(q13;q32) in 2 out of 3 MM (Calasanz et al., 1997; Smadja et al., 2001) and 1 patient with MCL (Fan & Rizkalla 2003), 14q32/ t(14;18)(q32;q21) in 4 lymphomas (Kobayashi et al., 1993; Horsman et al., 2001; Le Baccon et al., 2001; Fan & Rizkalla 2003) and highly complex karyotypes in the remaining patients.
In the group of patients with 1q21-25 breakpoints, it was a sole anomaly in 1 ALL (Strefford et al., 2007) and 1 MM (Nakano et al., 2005) and found with t(1;19)(q23;p13)/der(19)t(1;19)(q23;p13) in the remaining 2 ALL patients (Schmiegelow et al., 2012; Safavi et al., 2015); found as a part of highly complex karyotypes in lymphoma patients.

Result of the chromosomal anomaly

Fusion Protein
Oncogenesis Unbalanced 1q translocations with an acrocentric recipient chromosome 15 result in 1q trisomy. The main consequence of these rearrangements is genomic imbalance resulting from the presence of an extra copy of the long arm of chromosome 1, leading to overexpression of several genes, likely implicated in neoplastic processes by a gene dosage effect. They presumably occur as a secondary aberration in addition to well-known primary abnormalities, therefore representing clonal evolution preceding or accompanying disease progression.


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This paper should be referenced as such :
Zamecnikova A
der(15)t(1;15)(q11-12;p11-13) and der(15)t(1;15)(q21-25;p10-13);
Atlas Genet Cytogenet Oncol Haematol. in press
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