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

2016-02-01 Soad Al Bahar , Adriana Zamecnikova Affiliation

1.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.

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.

Bibliography

Pubmed ID	Last Year	Title	Authors

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/css/lib/bootstrap.min.css