der(1)t(1;1)(p36;q11-q32) in hematopoietic malignancies

2016-06-01   Adriana Zamecnikova  , Soad Al Bahar  

1.Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait; annaadria@yahoo.com

Abstract

Review on der(1)t(1;1)(p36;q11-q32) in hematopoietic malignancies, with data on clinics, and the genes involved.

Clinics and Pathology

Disease

Chronic myeloproliferative neoplasms (MPN), acute myeloid leukemia, acute lymphoblastic leukemia (ALL) and multiple myeloma (MM).

Phenotype stem cell origin

34 patients, mainly myeloid malignancies (19 cases). 10 patients had lymphoid malignancies (8 ALL, 1 chronic lymphocytic leukemia (CLL) and 1 plasma cell leukemia (PCL) and there were 5 MM cases (Table 1).
Chronic myeloproliferative neoplasms 5 patients: 1 polycythemia vera (PV) who progressed to myelofibrosis (MF) 27 years later (Duhoux et al., 2011), 1 chronic eosinophilic leukemia (CEL) (Duhoux et al., 2011), 1 chronic myeloid leukemia (CML) (Phan et al., 2006) and 2 patients with myelodysplastic syndrome (MDS) (Caramazza et al., 2010; Duhoux et al., 2011).
Acute myeloid leukemia 14 patients, mainly with myelomonocytic-lineage: 1 acute myeloblastic leukemia with maturation (Fugazza et al., 1997), 2 acute myelomonocytic leukemia (Michalova et al., 1999; Duhoux et al., 2011), one of them progressed from MDS (Michalova et al., 1999). From the 6 acute monocytic leukemia cases (Chessells et al., 2002; Picos-Cardenas et al., 2002; Scrideli et al., 2005; Noguchi et al., 2007; Duhoux et al., 2011; Sarova et al 2013), 1 progressed from MDS (Duhoux et al., 2011), 1 was a case with Down syndrome (DS) (Picos-Cardenas et al., 2002) and there were 2 infants (Chessells et al., 2002; Scrideli et al., 2005), one of them with partial trisomy 1q syndrome (Scrideli et al., 2005). 1 patient was diagnosed with acute megakaryoblastic leukemia (Preiss et al., 2006) and there were 4 AML unspecified patients (Duhoux et al., 2011; Blink et al 2012), 3 of them infants, among them one with DS (Blink et al., 2012).
Acute lymphoblastic leukemia 8 patients (Shikano et al.,1994; Uckun et al 1998; Bruch et al 2003; Paulsson et al 2010; Schmidt-Hieber et al 2010; Duhoux et al 2011; Subramaniyam et al 2011; Safavi et al 2015) with predominantly B-cell phenotype. There were 5 children (Shikano et al.,1994; Uckun et al 1998; Paulsson et al 2010; Duhoux et al., 2011) , one of them an infant patient (Bruch et al., 2003).
Various B-cell hematological neoplasms: 5 MM (Rajkumar et al., 1999; Bang et al., 2006; Vekemans et al., 2010; Sawyer et al., 2014), 1 CLL (Nordgren et al., 2000) and 1 plasma cell leukemia (Bastard et al.,1991) patient.
Table 1. Reported patients with der(1)t(1;1)(p36;q11-32).

Age / Sex

Disease

der(1)t(1;1)(p36;q11-q32)

Ref.

Chronic myeloproliferative neoplasms

F/40

CML

47,XX,der(1)t(1;1)(p36;q31),del(3)(p21p23),add(4)(q35),+der(7)add(7)(p22)add(7)(q33),-8,
t(9;22)(q34;q11),add(10)(p13),+mar

1

M/68

MDS

47,XY,+11/46,XY,der(1)t(1;11)(p36;q13)

2

F/60

CEL

46,XX,der(1)t(1;1)(p36;q12)/46,XX,der(13)t(1;13)(q12;p13)/46,XX,der(22)t(1;22)(q12;p13)

3

M/48

MDS

46,XY,der(1)t(1;1)(p36;q12)

4

M/75

PV-MF

48,XY,+8,+9/48,idem,der(1)t(1;1)(p36;q12)

5

Acute myeloid leukemia

F/68

AML-M2

45,XX,der(1)t(1;1)(p36;q11),-5,-7,-11,der(17)t(17;18)(p13;q11),+r,+mar/44,XX,-5,-7,-17,+mar,
dmin amplified c-MYC sequences

6

M/64

MDS-AML-M4

46,XY,del(5)(q22q33)    At diagnosis
46,XY,r(18)

45,XY,der(1)t(1;11)(p36;q23),-11,dmin    During transformation

46,XY,dmin

7

M/0

AML-M5

46,XY,der(1)t(1;1)(p36;q21)/45,idem,-Y/47,idem,+8/46,XY,der(21)t(1;21)(q21;p11)

8

M/3

AML-M5

46,XY,der(1)t(1;1)(p36;q32),-7,+21c/46,idem,del(9)(p22)

9

F/1

AML-M5

46,XX,der(1)t(1;1)(p36;q32),der(6)t(6;8)(p25;q13),+11,der(11;18)(q10;q10)dup(1)(q23q44)
Partial trisomy 1q "syndrome"

10

F/60

AML-M7

62,XX,-X,der(1)t(1;1)(p36;q22),-2,-3,-4,-5,-7,der(7)t(1;7),+8,-9,-11,-13,-14,der(14)t(5;7;14),
der(14)t(14;22)(p11;q11),+15,-16,-20,-21

11

M/25

AML-M5a

46,XY,der(1)t(1;1)(p36;q21)    DUSP10-PRDM16 fusion

12

F/1

AML

46,XX,der(1)t(1;1)(p36;q21)    Telomeric 1p36 probes deleted

13

M/1

AML

47,XY,der(1)t(1;1)(p36;?q31),+21c    Telomeric 1p36 probes deleted

14

M/65

AML

45,XY,der(1)t(1;1)(p36;q25),-5,-5,-9,add(17)(p13),der(21)t(5;21)(q11;q22),+2mar

15

F/65

AML-M5

46,XX,der(1)t(1;1)(p36;q22)    Telomeric 1p36 probes deleted

16

M/60

AML-M4

46,XY,der(1)t(1;1)(p36;q12)

17

F/1

AML

47,XX,der(1)t(1;1)(p36;q21),t(5;6)(p15;p23),+21c

18

F/50

AML-M5

46,XX,der(1)t(1;1)(p36;q12),t(9;11)(p22;q23)u2020

19

Acute lymphoblastic leukemia

M/4

T-ALL

46,XY,der(1)t(1;1)(p36;q21),del(4)(q31),add(12)(q24),t(14;18)(q22;q21)

20

M chi

ALL

46,XY,der(1)t(1;1)(p36;q21),t(9;22)(q34;q11)

21

F/0

B-ALL

46,XX,der(1)t(1;1)(p36;q11),ins(11;2)(q23;q11q11)    MLL-LAF4 fusion

22

M/12

B-ALL

55,XY,der(1)t(1;1)(p36;q21),+4,+4,+6,+10,+14,+17,+18,+21,+21/56,idem,+8

23

M

B-ALL
Post BMT relapse

45-46,XY,der(1)t(1;1)(p36;q21),t(3;5;10)(p13;q34;p13),t(6;21)(q21;q22),
der(8)t(8;8)(p21;q23),-9,t(9;22),-17/45-46,XY,der(1),t(3;16)(p13;q22),add(4)(q22),t(5;14)(q35;q11),
der(8),-9,t(9;22),add(10)(q24),add(11)(p11),-17,+der(22)t(9;22)x2

24

M/3

B-ALL

55,XY,der(1)t(1;1)(p36;q12),add(2)(p?),+4,+6,+10,+14,+16,+18,+21,+21,+mar/63-64,idem,+X,+5,+9,+11,+12,+15,+17,+19,+22    Telomeric 1p36 probes deleted

25

M/65

B- ALL

50-51,X,+X,-Y,der(1)t(1;1)(p36;q32),der(1)t(1;12)(q32;q15),der(4)del(4)(q21q25)t(4;6)
(p16;q13),i(6)(p10),+7,t(8;9)(q24;p13),der(10)t(8;10)(q24;p13),+11,der(12)t(12;18)(q24;q21)
t(14;18)(q32;q21)x2,dup(13)(q22q34)x2,t(14;18),der(17)t(8;17)(?;p13),der(18)t(10;18)(p?13;q?21),
der(18)t(14;18)x2 t(14;18)(q32;q21)

26

M/83

T-ALL

46,X,-Y,+del(X)(q26),der(1)t(1;1)(p36;q12)del(1)(q11q21),t(3;22)(q27;q11)/47,idem,+5     LN

27

Various hematological neoplasms

F/43

B-PCL

41,X,-X,der(1)t(1;1)(p36;q22),t(5;8)(q14;q24),del(6)(q11),
der(8)t(8;14)(p21;q11),-13,-14,-16,-18,-20,-20,+maru2020

28

F/53

MM

42-44,XX,del(1)(p32p34),der(1)t(1;1)(p36;q12),del(5)(p15),-8,-11,-12,-13,der(17)t(17;21)(p11;q11),-19,-20,-22,+5-6mar

29

M/57

CLL

44,X,Y,der(1)t(1;11)(p36;q13),der(2)t(2;6)(q33;q23),dic(3;6)(q10;p10),der(5)del(5)(p14)del(5)
(q31),der(7)t(Y;7)(q11;q21),der(8)t(8;11)(q22;?),del(11)(q12),der(12;14)t(12;14)t(11;14;12)
(q13;q32q10;q13),der(12)t(8;12),der(13)t(11;13)(q21;q34),der(17)t(17;18)(p13;q11),-18

30

F/46

MM

45,XY,del(1)(p12p22),der(1;16)(q10;p10),+der(1)t(1;1)(p36;q25),del(2)(q31),del(5)(q31),add(9)
(p24),der(12)t(1;12)(q12;q24),-13,del(14)(q22),add(17)(p13),+19,add(21)(p13),-22/46,idem,+18

31

M/70

MM

45,XY,del(1)(p13p32),-8,-13,der(14)t(1;14)(q12;q21),-20,+r,+mar/46,XY,del(1)(q25q43),der(1)
t(1;1)(p36;q21)del(1)(p11p32),ins(7;?)(q31;?),del(8)(q12),-13,der(14)t(1;14),-20,+2mar

32

M

MM

42-47,X,der(Y)t(Y;1)(q12;q12),del(1)(p12p22),der(1)t(1;1)(p36;q12)dup(1)(q12q44),t(4;5)
(p16;p13),t(8;22)(q24;q11),+12,del(12)(q14),-13,-14/53-63, idem,+1,-der(1),add(2)(q37),+3,+5,
+6,+7,+t(8;22),+9,+11,-14,+16,+20,incu2020

33

F

MM

46,X,-X,add(1)(q42),add(1)(p22),der(2)t(2;13)(p24;q12),+3,del(3)(p12p21),add(4)(p11),del(5)
(p13),+6,add(6)(q12),add(9)(q32),+11,der(12)add(12)(p13)add(12)(q24),der(12)add(12)(p11)?
dup(12)(q22q24)add(12)(q24),-13,-13,+15,del(17)(p11),+19,add(19)(p13),add(19)(p13)/46-47,
idem,add(15)(p13),-add(19)(p13)/48-49,idem,+X,-add(1)(p22),+der(1)t(1;1)(p36;q12),+2,
der(2)t(2;13),add(3)(q27),del(7)(q32),add(9),+del(9)(q12),+12,der(12),der(12),+add(12)(p13),
t(12;13)(q24;q12),+del(?13)(q12q22),-14,-add(19)(p13)u2020

34

Abbreviations: Ref., references; M., male; F., female; CML., chronic myeloid leukemia; MDS., myelodysplastic syndrome; CEL., chronic eosinophilic leukemia; PV., polycythemia vera; MF.,myelofibrosis; acute myeloid leukemia; AML-M2., acute myeloblastic leukemia with maturation., AML-M4., acute myelomonocytic leukemia., AML-M5., acute monoblastic leukemia; AML-M7., acute megakaryoblastic leukemia AML., acute myeloid leukemia; ALL., aAcute lymphoblastic leukemia/lymphoblastic lymphoma; BMT., bone marrow transplantation; PCL., plasma cell leukemia; MM., multiple myeloma; CLL., chronic lymphocytic leukemia.
1.Phan et al., 2006; 2.Caramazza et al., 2010; 3-5, 13-17,25.Duhoux et al., 2011; 6.Fugazza et al., 1997; 7.Michalova et al., 1999; 8.Chessells et al., 2002; 9.Picos-Cardenas et al., 2002; 10.Scrideli et al., 2005; 11.Preiss et al., 2006; 12.Noguchi et al., 2007; 18.Blink et al., 2012; 19.Sarova et al., 2013; 20.Shikano et al.,1994; 21.Uckun et al., 1998; 22.Bruch et al., 2003; 23.Paulsson et al., 2010; 24.Schmidt-Hieber et al 2010; 26.Subramaniyam et al., 2011; 27.Safavi et al., 2015; 28.Bastard et al.,1991; 29.Rajkumar et al., 1999; 30.Nordgren et al., 2000; 31.Bang et al., 2006; 32.Vekemans et al., 2010; 33-34.Sawyer et al., 2014.

Epidemiology

20 male and 14 female patients (sex ratio 1.4) with median age of 60 years (range 0 to 83 years). Balanced sex ratio in myeloid malignancies (10M/9F) and male prevalence in ALL cases (7M/1F, sex ratio 7). There were 10 pediatric cases (aged 0 to 12 years) in AML and ALL groups, 6 of them were infants (5 AML and 1 ALL cases).

Prognosis

Patients with 1p36 / PRDM16 translocations and/or terminal 1p36 deletions seems to have a poor prognosis despite a simple karyotype (Duhoux et al., 2011). In addition, there seems to be an over-representation of complex karyotypes that in association with an unbalanced rearrangement may reflect genomic instability correlated with an unfavorable outcome.

Cytogenetics

Cytogenetics morphological

Presents as one normal chromosome 1 and a der(1)t(1;1) chromosome, resulting in partial 1q trisomy. Heterogeneous cytogenetic presentation with q11-32 breakpoints on 1q.

Additional anomalies

Sole anomaly in 6 myeloid disorders: 1 MDS (Duhoux et al., 2011) and 5 AML (Noguchi et al 2007; Duhoux et al 2011). Two or several independent clones were found in 2 MPN (Caramazza et al., 2010; Duhoux et al., 2011) and 2 AML cases (Michalova et al., 1999; Chessells et al., 2002). Associated with chromosome 5 and/or 7 anomalies in 4 AML (Fugazza et al., 1997; Picos-Cardenas et al., 2002; Preiss et al., 2006; Duhoux et al., 2011) and with t(9;22)(q34;q11) in 1 CML (Phan et al 2006) and 2 ALL cases (Uckun etal 1998; Schmidt-Hieber et al 2010). Very complex karyotypes (≥5 abnormalities) were observed in 15 patients (Bastard et al.,1991; Fugazza et al., 1997; Rajkumar et al., 1999; Bang et al., 2006; Phan et al., 2006; Preiss et al., 2006; Nordgren et al., 2000; Schmidt-Hieber et al., 2010; Vekemans et al., 2010; Duhoux et al., 2011; Subramaniyam et al., 2011; Sawyer et al., 2014; Safavi et al 2015) while there seems to be an over-representation of complex anomalies in AML, ALL and B-cell hematological neoplasms.

Result of the Chromosomal Anomaly

Oncogenesis

The chromosomal translocation der(1)t(1;1)(p36;q11-q32) is a nonrandom event in both myeloid and lymphoid neoplasias (Lestou et al., 2003; Duhoux et al.,2012). While the cytogenetic presentation is heterogeneous and there is a marked variability in 1q and 1p36 breakpoints, the common impact of this rearrangement is duplication of 1q sequences through formation of an unbalanced translocation. In addition, 1p36 alterations are frequent in hematological malignancies, suggesting that the region is harboring gene(s) important in oncogenesis. One of the genes that may be functionally disrupted is the PRDM16 (PR domain containing 16; also known as MEL1 and MDS1/EVI1-like) gene, the main target of 1p36 rearrangements (Duhoux et al., 2012; Matsuo et al., 2015). Among them, PRDM16 have been found to be rearranged with the DUSP10 (dual specificity phosphatase 10) gene in der(1)t(1;1)(p36.3;q21) in AML (Noguchi et al.,2007), raising the possibility that PRDM16 may be activated by chromosomal rearrangements involving genes on 1q, at least in some patients. Other candidate genes that have been mapped in the 1p36 region are tumor suppressor genes that might be deleted as a consequence of the unbalanced rearrangement. Terminal 1p36 deletions are frequent in both myeloid and lymphoid malignancies, indicating inactivation of tumor suppressor genes may be the common oncogenic mechanism in these diseases (Duhoux et al., 2011). It is likely, that patients with der(1)t(1;1)(p36;q11-32) undergo mixed duplication and deletion events associated with formation of the unbalanced translocation.

Article Bibliography

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227759852012High frequency of copy number alterations in myeloid leukaemia of Down syndrome.Blink M et al
126610122003Occurrence of an MLL/LAF4 fusion gene caused by the insertion ins(11;2)(q23;q11.2q11.2) in an infant with acute lymphoblastic leukemia.Bruch J et al
203578212010Trisomy 11: prevalence among 22,403 unique patient cytogenetic studies and clinical correlates.Caramazza D et al
119869372002Clinical features, cytogenetics and outcome in acute lymphoblastic and myeloid leukaemia of infancy: report from the MRC Childhood Leukaemia working party.Chessells JM et al
220507632012PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies.Duhoux FP et al
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173219992007Dual-specificity phosphatase 10 is fused to MDS1/EVI1-like gene 1 in a case of acute myelogenous leukemia with der1t1;1(p36.3;q21).Noguchi M et al
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Summary

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Citation

Adriana Zamecnikova ; Soad Al Bahar

der(1)t(1;1)(p36;q11-q32) in hematopoietic malignancies

Atlas Genet Cytogenet Oncol Haematol. 2016-06-01

Online version: http://atlasgeneticsoncology.org/haematological/1644/gene-fusions-explorer/js/lib/img/logo-atlas-4.svg