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der(5)t(1;5)(q12-q25;q13-q35)

Written2016-02Adriana Zamecnikova, Soad al Bahar
Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait; annaadria@yahoo.com

Abstract Review on t(1;5)(q12-q25;q13-q35), with data on clinics.

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9808/3 Mixed phenotype acute leukaemia, B/myeloid, NOS 152
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9732/3 Plasma cell myeloma / Multiple myeloma
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 9716/3 Hepatosplenic T-cell lymphoma
ICD-Morpho 9700/3 Mycosis fungoides
ICD-Morpho 9690/3 Follicular lymphoma; Paediatric follicular lymphoma
Atlas_Id 1646

Clinics and Pathology

Disease Myeloid malignancies, acute lymphoblastic leukemia (ALL) multiple myeloma (MM), B- and T- cell lymphoma and sporadic cases of other malignancies.
Phenotype / cell stem origin Myeloid malignancies in 10 patients: 1 chronic myeloid leukemia (CML) (Dastugue et al., 1986), 3 myelodysplastic syndromes (MDS) (Furuya et al., 1992; Johansson et al., 1997; Quentin et al., 2011) and 6 acute myeloid leukemia (AML) cases (Gyger et al., 1989; Shikano et al., 1993; Wong et al., 1993; Borkhardt et al., 2000; Van Limbergen et al., 2002; Jekarl et al., 2010).
Acute lymphoblastic leukemia in 8 cases (Saikevych et al., 1991; Martin et al., 1996; Rieder et al., 1996; van den Berghe et al., 2000; Chang et al., 2006; Wehrli et al., 2009; Paulsson et al ., 2015; Safavi et al., 2015).
Multiple myeloma in 11 cases (Smadja et al., 2001; Smadja et al., 2003. Nilsson et al., 2002; Mohamed et al., 2007; Lim et al., 2013; Sawyer et al., 2014). B-cell neoplasms: follicular lymphoma in 3 (Le Baccon et al., 2001; Horsman et al., 2003; Johnson et al., 2008), diffuse large B-cell lymphoma in 4 (Jonveaux et al., 1990; Jerkeman et al., 1999; Yoshioka et al., 2005; Ruminy et al., 2006) and mature B-cell neoplasm (Tanaka et al., 2001) in 1 patient. T-cell neoplasms: reported in one case each of peripheral T-cell lymphoma (Schlegelberger et al., 1994), hepatosplenic T-cell lymphoma (Ott et al.,1998), and mycosis fungoides/Sezary syndrome (Perez-Vila et al., 2000).
Table 1. Reported cases with unbalanced chromosome translocations der(5)t(1;5) involving 1q12-q25 and 5q13-q35.

 

Sex/ Age

Disease

Karyotype

Myeloid malignancies

1

F/68

CML (biphenotypic blast phase)

46,XX,der(5)t(1;5)(q23;q32),t(9;22)(q34;q11),t(14;14)(q11;q32)

2

M/57

AML-M1

43,XY,-1,del(5)(q13q33),der(5)t(1;5)(q23;q33),-7,add(8)(p23),del(11)(p15),add(12)(p11),-14,-16,-17,+2mar

3

M/76

MDS

46,XY,der(5)t(1;5)(q21;q35)/46,XY,+der(1)t(1;7)(p11;p11),-7

4

F/0 

5

M/13

AML-M1

49,XX,+3,+der(5)t(1;5)(q21;q21),+22

6

M/64

MDS (Hodgkin disease, radiotherapy, chemotherapy)

46,XY,der(5)t(1;5)(q24;q14)

7

M/6

AML

46,XY,der(1)add(1)(p36)add(1)(q32),der(5)t(1;5)(q25;q22),add(6)(q15),del(7)(p14p15),del(17)(p12)

8

M/76

AML-M2

45,XY,der(1)t(1;5)(q21;q33),der(3)t(3;6)(q21;q22),der(?3)r(3;6),der(5)t(1;5)(q21;q13),-18

9

F/21

AML-M1

46,XX,der(5)t(1;5)(q12;q35),t(16;21)(p11;q22)/46,idem,t(1;7)(p32;p22)/46,idem,del(6)(q23)/48,XX,+7,+8,t(16;21)

10

M/5

MDS (Fanconi anemia)

46,XY,der(5)t(1;5)(q12;q14)

Acute lymphoblastic leukemia

11

F/70

BAL

46,XX,t(9;22)(q34;q11)/46,idem,der(5)t(1;5)(q22;q35)/46,idem,der(6)t(1;6)(q22;q27)

12

M

ALL

59,XXY,+Y,-1,-2,-3,der(5)t(1;5)(q21;q21),-7,-9,-11,-12,-13,-16,-19,-20,+21,-22

13

M/57

B-ALL

48,XY,der(5)t(1;5)(q12-21;q35),+8,-9,t(9;22)(q34;q11),+14,+der(22)t(9;22)

14

M

ALL

58,XXY,-1,-2,-3,der(5)t(1;5)(q23;q31),-7,-8,-9,+10,-11,-12,-13,-15,-16,+18,-19,-20

15

M/4

ALL

51-55,XY,+der(5)t(1;5)(q12;q31),+6,+10,+18,+18,+21,+21

16

M/9

ALL

47,X,-Y,+der(5)t(1;5)(q21;q31),-8,del(9)(p13),+13,+mar

17

M/2

ALL

62,XY,+X,+Y,+der(5)t(1;5)(q12;q21),+6,+8,+9,+10,+11,+12,+14,+14,+17,+18,+21,+21,+22

18

F/22

ALL

46,XX,t(1;5)(q21;q32)/42-48,idem,+8/48,idem,+der(5)t(1;5),+21

Multiple myeloma

19

M

MM

50,X,-Y,del(1)(p22p31),+3,+der(5)t(1;5)(q12;q35),+7,+9,del(11)(p11p12),add(12)(p13),-13,-14,+15,+19,-22,+2mar/49,idem,-5

20

M

MM

59,X,del(Y)(q12),-X,-1,t(1;8)(q31;q24),-2,der(2)t(1;2)(q12;q32),-4,der(5)t(1;5)(q13;q34), dic(6;12)(q11;p12),-7,-8,-10,del(11)(p12p14),-12,-13,-13,-14,-16,add(16)(p12),dic(17;?)(q25;?),-20,+21,+21,-22,+2mar

21

F/51

MM

45,XX,del(1)(p22p32),der(5)t(1;5)(q25;q35),-10,t(11;14)(q13;q32),ins(13;12)(p11;q22q24),del(14)(q22)

22

F/74

MM M

44,X,-X,-1,inv(2)(p13q37),der(5)t(1;5)(q21;q35),der(6)t(1;6)(q21;q21),+del(11)(q21),-13,-14,der(17)(1;17)(p31;p13),+18,-20

23

F/39

MM 

50,X,-X,+add(3)(q27),-4,+der(5)t(1;5)(q21;q35),+add(6)(q27),+del(7)(q32),t(8;22)(q24;q11),del(13)(q12q21),add(14)(q32),+15,+19

24

F/43

MM M

46,XX,add(1)(p22),del(3)(p24),-5,der(5)t(1;5)(q13;q31),-8,-14,add(17)(p13),add(19)(p13),+1-4mar

25

F

MM

42,X,-X,del(1)(p13p32),der(2)t(1;2)(q21;q25),del(4)(q31),t(8;13)(q24;q11),del(12)(p11),-13,-21/42,idem,der(5)t(1;5)(q21;q35),add(15)(p13),add(19)(q13)

26

F

MM

44,XX,+del(3)(q21q25),der(5)t(1;5)(q21;q35),der(8;14)(q10;q10),+der(8;14)(q10;q10),der(12;15)(q10;q10),-13,del(14)(q22q32),-22

27

M

MM

52-54,XY,der(1)t(1;8)(q21;q11)ins(1;?)(q21;?),add(1)(p22),der(2)t(2;8)(q37;q13),+5,+5,der(5)t(1;5)(q21;q22)x2,+7,der(7)del(7)(p12p13)t(1;7)(p?22;q36),+8,del(8)(p11),+9,t(9;12)(p10;p10),+11,+15,?t(16;22)(p12;q13),der(19)t(17;19)(q11;p13),+21,+22/55-56,idem,+7,+del(8)(p11),+12

28

M

MM

41-42,Y,der(X)t(X;1)(p22;q12),del(1)(p11p22),t(1;3)(p13;p25),-2,del(2)(q?33),-4,der(5)t(1;5)(q12;q35),t(6;22)(p12;p11),del(12)(p12p12),-13,add(17)(p11),-20/39-42,idem,-del(1),+der(1)del(1)(p11p22)t(1;11)(q?44;q12)ins(1;?)(q?21;?),ins(?11;?)(q12;?)

29

M

MM

82-92,XXY,-Y,-1,-1,der(1)add(1)(p36)add(1)(q42),-2,-2,del(3)(q21)x2,-4,-4,add(5)(q15),der(5)t(1;5)(q12;q15),add(6)(q21)x2,+7,+7,+7,add(7)(p22),add(7)(q36),der(7)t(1;7)(q12;q32)x3,+8,der(8)t(1;8)(q12;q22)x2,+9,+9,add(9)(p24),der(9)t(1;9)(q12;q34),der(10)t(1;10)(q12;q26),add(11)(p15)x2,-12,-13,del(?13)(q12q22)x3,-14,der(14)t(1;14)(p11;q32)x3,-15,-15,add(15)(p11),add(16)(q24),-17,add(17)(p11)x2,+19,+19,-20,+21,add(21)(p11),+22,add(22)(q13),inc

Other malignancies

30

F/56

DLBCL LN

52,XX,add(1)(q32),add(3)(q29),+der(5)t(1;5)(q23;q13),del(7)(p13),del(11)(q21),t(11;14)(q22;q32),+add(18)(q23),+4mar

31

F/69

PTCL LN

101-107,XX,der(X;6)(p10;p10)x2,del(2)(p22),t(2;3)(q35;q29),der(3)t(3;22)(p22;q12)x3,+del(4)(q25q34),del(5)(q22q24)x2,+der(5)t(1;5)(q22;q13),+dup(6)(p2?1p12),+7,+der(7)t(7;7)(q21;p12),+add(9)(q21)x2,der(9)t(4;9)(q34;q21)x2,der(9;20)(p10;p10)x2,-10,-10,+ins(11;?)(q12;?),t(11;14)(p13;q11),+12,del(13)(q14q31)x2,del(14)(q21q31),+21,+21,+der(22)t(18;22)(q12;q12)x2,+mar

32

M/28

HTCL LN

46,XY,del(1)(q25),der(5)t(1;5)(q25;q31),der(9)t(9;13)(p23-24;?q14),del(13)(q12)

33

F/65

DLBCL LN

69-87,XXX,+1,del(1)(q22)x2,-4,+der(5)t(1;5)(q22;q15),-6,+7,+9,+11,+12,+13,t(14;18)(q32;q21)x2,+15,+16,+16,+17,-18,+19,+19,+19,+20,-22,+2-5mar

34

F/94

MF/SS T-lineage LN

44-45,XX,der(2)t(2;12)(p25;q11),der(5)t(1;5)(q25;q35),-9,-10,-13,der(14)t(6;14)(p21;p11),der(15)t(8;15)(q?;q26),der(17)t(13;17)(q?;q25),i(17)(q10),add(20)(q13),+21/44-45,XX,der(2)t(2;12),der(3)ins(3;3)(p26;q22q29)t(1;3)(q32;q22),del(5)(q13),+der(8)t(4;8)(q25;q21) t(4;8)(q35;p21),-9,-10,der(14)t(6;14),-15,-17,i(17)(q10),+21

35

F/72

MBCN

49,XX,-1,der(2)t(2;11)(q21;q21-22),+5,+der(5)t(1;5)(q21;q31),del(6)(q13q15),-8,add(14)(q32),+18,+der(?)t(?;12)(?;q21)x2

36

M/41

FL 

37

F/43

FL LN

47,XX,t(1;16)(p34;q24),ins(2;?)(p13;?),+der(5)t(1;5)(q24;q33),ins(7;?)(q22;?),ins(12;?)(q15;?)

38

M

DLBCL LN

46,XY,der(1)t(1;13)(q32;q14),t(3;14)(q27;q32),der(5)t(1;5)(q25;q13),der(6)(1;6)(q25;q21),del(7)(q22q32),add(8)(p21),del(8)(q22),inv(9)(p13q13),der(13)t(8;13)(q22;q12)

39

M

DLBCL LN

54,XY,+X,+2,t(3;14)(q27;q32),+der(5)t(1;5)(q21;q13)x2,+del(6)(q12q27),+7,+11,+12,+add(17)(q21)

40

F

FL LN

47,XX,t(1;16)(p34;q24),ins(2;?)(p13;?),+der(5)t(1;5)(q24;q33),ins(7;?)(q22;?),ins(12;?)q15;?)



1. Dastugue et al., 1986; 2. Gyger et al., 1989; 3. Furuya et al., 1992; 4. Shikano et al., 1993; 5. Wong et al., 1993; 6. Johansson et al., 1997; 7. Borkhardt et al., 2000; 8. Van Limbergen et al., 2002; 9. Jekarl et al., 2010; 10. Quentin et al., 2011; 11. Saikevych et al., 1991; 12. Martin et al., 1996; 13. Rieder et al., 1996; 14. van den Berghe et al., 2000; 15. Chang et al., 2006; 16. Wehrli et al., 2009; 17. Paulsson et al ., 2015; 18. Safavi et al., 2015; 19. Smadja et al., 2001; 20. Smadja et al., 2003. 21. Nilsson et al., 2002;  22-24. Mohamed et al., 2007; 25-26. Lim et al., 2013; 27-29. Sawyer et al., 2014; 30. Jonveaux et al., 1990; 31. Schlegelberger et al., 1994; 32. Ott et al.,1998; 33. Jerkeman et al., 1999; 34. Perez-Vila et al., 2000; 35. Tanaka et al., 2001; 36. Le Baccon et al., 2001; 37. Horsman et al., 2003; 38.Yoshioka et al., 2005; 39. Ruminy et al., 2006; 40. Johnson et al., 2008.

M., male; F., female; CML., chronic myeloid leukemia; AML-M1., acute myeloblastic leukemia without maturation; MDS., myelodysplastic syndrome; AML-M0., acute myeloblastic leukemia with minimal differentiation; AML., acute myeloid leukemia; AML-M2., acute myeloblastic leukemia with maturation; BAL., bilineage or biphenotypic leukemia; ALL., acute lymphoblastic leukemia; MM., multiple myeloma; DLBCL., diffuse large B-cell lymphoma; LN., lymph node; PTCL., peripheral T-cell lymphoma ; HTCL., hepatosplenic T-cell lymphoma; MF/SS., mycosis fungoides/Sezary syndrome; MBCN., mature B-cell neoplasm; FL., follicular lymphoma.

Epidemiology At least 40 reported cases; balanced sex ratio (22M/18F aged 0 to 76 years). Male prevalence in myeloid (7M/3F, aged 0 to 76 years) and ALL cases (6M/2F, aged 2 to 70 years). There were 5 males and 6 female MM patients (aged 39 to 73 years) and 4M/7F cases in other malignancies group (aged 28 to 90 years) (Table 1).
Prognosis The prognosis is likely unfavorable in association with poor-risk genetic features and complex karyotypes.

Cytogenetics

Cytogenetics Morphological Unbalanced translocation, characterized by the presence of 2 copies of normal chromosome 1, only 1 copy of normal chromosome 5 and a derivative chromosome 5, containing 1q. Presents as 2 normal chromosomes 1 and 5 and a +der(5)t(1;5) chromosome in 14 out of 40 cases. The breakpoints in 1q varied from 1q12 to q25 and were located on 5q13-q35.
Additional anomalies Appears as a sole chromosomal abnormality in 2 MDS patients: in a 5-years old boy with Fanconi anemia (Quentin et al., 2011) and in a 64-years old male who received therapy for Hodgkin disease (Johansson et al., 1997). Found in association with t(9;22) in a CML (Dastugue et al., 1986) and in 2 ALL cases (Saikevych et al., 1991; Rieder et al., 1996). Presents as a sole structural abnormality in association with numerical anomalies in 5 out of 8 ALL cases (Martin et al., 1996; van den Berghe et al., 2000; Chang et al., 2006; Paulsson et al ., 2015; Safavi et al., 2015) and complex karyotypes in the remaining patients. Associated with additional unbalanced chromosome 1q abnormalities in 3 myeloid (Furuya et al., 1992; Shikano et al., 1993; Van Limbergen et al., 2002), 1 ALL (Saikevych et al., 1991), 6 MM (Smadja et al., 2003; Mohamed et al., 2007; Lim et al., 2013; Sawyer et al., 2014) and 2 lymphoma patients (Le Baccon et al., 2001; Yoshioka et al., 2005).

Genes involved and Proteins

Note The balanced t(1;5)(q21;q33) results in TPM3 / PDGFRB and the t(1;5)(q23;q33) in PDE4DIP /PDGFRB fusion that are sensitive to inhibition with imatinib (Wilkinson et al., 2003; Rosati et al., 2006; Cheah et al., 2014) in chronic myeloproliferative disorders

Result of the chromosomal anomaly

Fusion Protein
Oncogenesis Unbalanced translocations between 1q and 5q are chromosomal abnormalities detectable in a broad spectrum of haematological malignancies including both lymphoid and myeloid neoplasms. Although cytogenetically heterogeneous, the main consequence of this rearrangement is a genomic imbalance resulting from gain of genes on 1q associated with partial 5q monosomy. Trisomies of genes located on the long arm of chromosome 1 are likely be implicated in neoplastic processes by a gene dosage effect resulting in overexpression of several genes. Alternatively, effects of the concomitant partial aneuploidy of genes on the partner chromosome 5 may play a role. Deletion of genes located on the long arm of chromosome 5 is a well-known chromosomal abnormality in myeloproliferative malignancies, therefore loss of the genes from 5q may be involved in neoplastic transformation and/or disease progression in these disorders. Although der(5)t(1;5)(q12-q25;q13-q35) was found as the sole abnormality in 2 patients, it usually presents with primary abnormalities such as t(9;22), 5q-, trisomy 8, monosomy 7 in myeloid malignancies, hyperploidy in ALL, complex karyotypes in MM and lymphomas, therefore it is apparently a secondary event preceding or accompanying disease evolution. The observation of this anomaly in highly complex karyotypes may be predictive of unfavorable prognosis in hematologic malignancies.
  

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Citation

This paper should be referenced as such :
Zamecnikova A, al Bahar S
der(5)t(1;5)(q12-q25;q13-q35);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/der5t0105ID1646.html


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