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

2016-02-01   Soad Al Bahar  , Adriana Zamecnikova  

1.Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait; [email protected]

Abstract

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

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 stem cell 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

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.

Article Bibliography

Pubmed IDLast YearTitleAuthors
109086482000The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q.Borkhardt A et al
168492812006Cytogenetics in childhood acute lymphoblastic leukemia in Taiwan: a single-institutional experience.Chang HH et al
246870852014Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib.Cheah CY et al
34894951986t(14;14)(q11;q32) in biphenotypic blastic phase of chronic myeloid leukemia.Dastugue N et al
29248861989Translocation (1;5)(q23;q33) in adult acute non-lymphocytic leukemia.Gyger M et al
125809562003Follicular lymphoma lacking the t(14;18)(q32;q21): identification of two disease subtypes.Horsman DE et al
206948422010CD56 antigen expression and hemophagocytosis of leukemic cells in acute myeloid leukemia with t(16;21)(p11;q22).Jekarl DW et al
100898961999Prognostic implications of cytogenetic aberrations in diffuse large B-cell lymphomas.Jerkeman M et al
93988621997Translocations between the long arms of chromosomes 1 and 5 in hematologic malignancies are strongly associated with neoplasms of the myeloid lineages.Johansson B et al
187205232008Prognostic significance of secondary cytogenetic alterations in follicular lymphomas.Johnson NA et al
22531891990Deletion of (7p13p14) in non-Hodgkin's lymphoma.Jonveaux P et al
115794652001Novel evidence of a role for chromosome 1 pericentric heterochromatin in the pathogenesis of B-cell lymphoma and multiple myeloma.Le Baccon P et al
236731022013Cytogenetic and molecular aberrations of multiple myeloma patients: a single-center study in Singapore.Lim AS et al
88461211996Comparison of fluorescence in situ hybridization, cytogenetic analysis, and DNA index analysis to detect chromosomes 4 and 10 aneuploidy in pediatric acute lymphoblastic leukemia: a Pediatric Oncology Group study.Martin PL et al
176546862007Chromosome aberrations in a series of 120 multiple myeloma cases with abnormal karyotypes.Mohamed AN et al
122253922002Cytogenetic features of multiple myeloma: impact of gender, age, disease phase, culture time, and cytokine stimulation.Nilsson T et al
95374801998Abdominal T-cell non-Hodgkin's lymphoma of the gamma/delta type in a patient with selective immunoglobulin A deficiency.Ott MM et al
108971402000A new case of Sézary cell leukemia: a morphological variant of prolymphocytic leukemia.Pérez-Vila Mf et al
259619402015The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia.Paulsson K et al
213255962011Myelodysplasia and leukemia of Fanconi anemia are associated with a specific pattern of genomic abnormalities that includes cryptic RUNX1/AML1 lesions.Quentin S et al
89820451996Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia.Rieder H et al
168380282006TPM3/PDGFRB fusion transcript and its reciprocal in chronic eosinophilic leukemia.Rosati R et al
166190462006Two patterns of chromosomal breakpoint locations on the immunoglobulin heavy-chain locus in B-cell lymphomas with t(3;14)(q27;q32): relevance to histology.Ruminy P et al
252610972015Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia.Safavi S et al
20339591991Multiparameter analysis of acute mixed lineage leukemia: correlation of a B/myeloid immunophenotype and immunoglobulin and T-cell receptor gene rearrangements with the presence of the Philadelphia chromosome translocation in acute leukemias with myeloid morphology.Saikevych IA et al
244975332014Jumping translocations of 1q12 in multiple myeloma: a novel mechanism for deletion of 17p in cytogenetically defined high-risk disease.Sawyer JR et al
79878001994Recurrent chromosome abnormalities in peripheral T-cell lymphomas.Schlegelberger B et al
82754491993Jumping translocations of 1q in Burkitt lymphoma and acute nonlymphocytic leukemia.Shikano T et al
115680112001Hypodiploidy is a major prognostic factor in multiple myeloma.Smadja NV et al
145066972003Further cytogenetic characterization of multiple myeloma confirms that 14q32 translocations are a very rare event in hyperdiploid cases.Smadja NV et al
111653192001Restricted chromosome breakpoint sites on 11q22-q23.1 and 11q25 in various hematological malignancies without MLL/ALL-1 gene rearrangement.Tanaka K et al
117469882002Identification of cytogenetic subclasses and recurring chromosomal aberrations in AML and MDS with complex karyotypes using M-FISH.Van Limbergen H et al
191676092009Non-classical karyotypic features in relapsed childhood B-cell precursor acute lymphoblastic leukemia.Wehrli LA et al
129074572003Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinib.Wilkinson K et al
83425411993Terminal acute myelogenous leukemia in a patient with congenital agranulocytosis.Wong WY et al
155436002005Cytogenetic features of de novo CD5-positive diffuse large B-cell lymphoma: chromosome aberrations affecting 8p21 and 11q13 constitute major subgroups with different overall survival.Yoshioka T et al
111567372000Static cytometry identifies hyperdiploid childhood ALL.van den Berghe JA et al

Summary

Class disease

NHL

Citation

Soad Al Bahar ; Adriana Zamecnikova

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

Atlas Genet Cytogenet Oncol Haematol. 2016-02-01

Online version: http://atlasgeneticsoncology.org/haematological/1646/der(5)t(1