i(X)(p10) in female patients

2016-12-01   Tatiana Gindina 

1.R.M. Gorbacheva Research Institute of Pediatric Oncology Hematology and Transplantation at First Saint-Petersburg State Medical University named I.P.Pavlov, Saint-Petersburg, Russia / tatgindina@gmail.com

Abstract

Review on i(X)(p10) in female patients

Clinics and Pathology

Disease

i(X)(p10) occurs in a wide spectrum of hematologic malignancies, in both myeloid and lymphoid disorders, including MDS, CMML, CML, de novo and therapy-related AML, ALL, NHL and Hodgkin lymphoma.
Myelodysplastic syndrome (MDS) was diagnosed in 7 patients (Adeyinka et al., 2007), 2 of them with refractory anaemia with ring sideroblasts (RARS) (Knuutila et al., 1984; Dewald et al., 1989), one patient with refractory anaemia (RA) (Adeyinka et al., 2007) and one with refractory anaemia with excess blasts (RAEB)(Sato et al., 2002).
Chronic myelomonocytic leukaemia (CMML): 3 patients (MacGrogan et al., 2004; Chen et al., 2010; Nacheva et al., 1995).
Chronic myeloid leukemia (CML): 2 patients (Selleri et al., 1989; Barbouti et al., 2002).
Acute myeloid leukemia (AML): there were 8 patients with different variants of AML: 1 AML-M1 (Fitzerald et al., 1983), 1 AML-M2 (Dewald et al., 1989), 1 AML-M4 (Bao et al., 2006), 2 therapy-related AML (Preiss et al., 2010; Adeyinka et al., 2007).
Acute lymphoblastic leukemia (ALL): 3 patients. Two of them with relapse after chemotherapy (Adeyinka et al., 2007) and allo-HSCT (Gindina, own case, table 1, #23), one patient with Down syndrome (Baker et al., 2003).
Hodgkin lymphoma, nodular sclerosis (HL) was diagnosed in 2 patients (Falzetti et al., 2005; Schlegelberger et al., 1994).
Non Hodgkin lymphoma (NHL): 1 patient (Temperani et al., 1995).
Mantle cell lymphoma (MCL): 1 patient (Gindina, own case, table 1, #25).
Cytopenias: 3 patients (Adeyinka et al., 2007), 2 of them with anaemia, one with thrombocytopenia.

Epidemiology

i(X)(p10) is observed as the sole abnormality in myeloid malignancies and has been demonstrated in females of advanced age. Nonetheless, this abnormality has been observed seldom in younger patients with AML, ALL, Hodgkin lymphoma, NHL. The median age of female patients is 60 years (range, 3 - 83 years).
Table 1. Reported cases with i(X)(q10).
#

Age, gender

DiseaseKaryotypeAuthor
1

32, F

CML46,XX,t(9;22)(q34;q11)(8)/47,X,i(X)(p10),t(9;22),+22(8)/48,i(X)(p10)x2,+X,t(9;22),+22(16)Selleri et al, 1989
2

50, F

CML46,X,i(X)(p10),t(9;22)(q34;q11),i(17)(q10)(9)/50,idem,+1,+8,+13,+19(2)Barbouti et al, 2002
3

62, F

RA46,X,i(X)(p10)(5)/46,XX(15) Adeyinka et al, 2007
4

76, F

RARS 46,X,i(X)(p10)(22)Knuutila et al, 1984
5

74, F

RARS46,X,i(X)(p10)(3)/47,idem,+idic(X)(q13)(2)/47,X,idic(X),+idic(X)(4)/46,XX(10) Dewald et al, 1989
6

87, F

RAEB46,X,del(X)(q22q26),+i(X)(p10),t(1;3)(p36;p21),der(6)del(6)(p23p25)del(6)(q1?5q2?5),add(7)(q32),-8, add(9)(p?11),add(11)(q23),t(12;13)(q11;q12),-14,+16,-18,inv(19)(p13q11),+mar(2)/47,idem, +add(14)(q32)(3)/46,idem,der(1)t(1;3)t(1;14)(p32;q32),der(3)t(1;3),der(14)t(1;14)(2)/46,idem, der(1),t(1;3), der(3),der(14),add(17)(p1?3)(2)/46,XX(21)Sato et al, 2002
7

73, F

MDS46,X,i(X)(p10),del(5)(q13q33)(6)/46,XX(14) Adeyinka et al, 2007
8

80, F

MDS46,X,i(X)(p10)(2)/46,XX(19)Adeyinka et al, 2007
9

38, F

MDS46,X,i(X)(p10)(2)/46,XX(18)Adeyinka et al, 2007
10

?, F

CMML46,X,i(X)(p10)(20)MacGrogan et al, 2004
11

?, F

CMML46,X,i(X)(p10)Chen et al, 2010
12

75, F

CMML46,X,i(X)(p10)(3)/46,idem,del(20)(q11q13)(28)Nacheva et al, 1995
13

74, F

AML47,X,i(X)(p10)x2(3)/48,idem,+8(21)/49,idem,+20(8)Hagemeier et al, 1981
14

79, F

AML, M147,X,i(Xp10)x2(22) Fitzgerald et al, 1983
15

83, F

AML, M246,X,idic(X)(q13)(3)/47,idem,+idic(X)(2)/46,X,i(X)(p10)(2)46~50,X,i(X)(p10),+8,+2mar(3)/46,XX(4) Dewald et al, 1989
16

74, F

AML, M446,X,i(X)(p10)(5)/46,XX(7)Bao et al, 2006
17

?, F

AML46,XX,inv(3)(q21q26)(1)/45,idem,-7(11)/45,idem,i(X)(p10),-1(8)Lugthart et al, 2010
18

32, F

AML47~50,XX,+i(X)(p10)x2,+8,+9(cp16)/46,XX(5)Adeyinka et al, 2007
19

68, F

t-AML, M1 46,XX,del(20)(q11)(5)/45,X,i(X)(p10),-7,del(20)(q11)(20)Preiss et al, 2010
20

62, F

t-AML 46,X,i(X)(p10)(17)/46,XX(3)Adeyinka et al, 2007
21

3, F

ALL48,XX,+i(X)(p10),+21c(12)/47,XX,+21c(10)Baker et al, 2003
22

17, F

ALL (relapse after CT) 45,X,-X,r(20)(10)/46,X,i(X)(p10),r(20)(7)/46,XX(3)Adeyinka et al, 2007
23

25, F

Common ALL (relapse after alloHSCT) 49,XX.ish+i(X)(p10),+1,t(1;7)(p13;q11),t(2;3)(p?;q?),der(5)t(5;8)(q?;?),+6,der(6)t(6;9)(p?;?)t(6;9)(q?;?)ins(6;13)(q?;q?q?),der(6)t(6;15)(q?;q?),del(7)(p?), +8,der(8)t(2;8)(?;q?), der(8)t(8;14)(p?;q?),-13,der(15)t(5;15)(?;q?),del(15)(q?),der(20)t(15;20)(?;q?)(17)(24XCyte) Gindina T
(own case)
24

65, F

NHL47,X,i(X)(p10),add(2p),add(14q),-19,+22,+r(5)/47,idem,del(6q),add(16)(q24)(11)Temperani et al, 1995
25

58, F

MCL44,-X,i(X)(p10),del(1)(q31),add(6)(q27),t(11;14)(q13;q32),-13,add(17)(q25),add(21)(p11)(12)/46,XX(8)Gindina T
(own case)
26

18, F

Hodgkin disease, nodular sclerosis59~83,XXX,-X,i(X)(p10), -1,del(1)(q?),+2,add(2)(q37)x3,+3,del(3)(q26),-6,del(7)(q12q22),del(7)(q35), +8,del(8)(q24),-9,-10,-11,-11,del(11)(q12q13),+12,-13,-13, -14,-15,-16,-17,-17,-18,+20,del(20)(q11q13), add(20)(q13),-21,+4mar(cp6)/46,XX(164)Falzetti et al, 1999
27

26, F

Hodgkin disease, nodular sclerosis81-85,XX,-X,i(X)(p10),del(1)(p21),+i(2)(p10)x2,del(3)(q21),del(4)(q?25),i(4)(p10),i(4)(q10),+5,-6,-7,del(7)(q32),i(7)(q10),del(9)(q21q31),der(12)t (3;12)(q21;q22),-13,-13,-15,+16,del(17)(p11),-18,-18,-20,add(20)(q13),-22,-22,-22,i(22)(q10),+mar(8)Schlegelberger et al. 1994
28

80, F

?46,X,i(X)(p10)(14) Adeyinka et al, 2007
29

74, F

?49,XX,+i(X)(p10),+8,+i(11)(q10)(17)/50,idem,+5(cp2)/46,XX(1)Adeyinka et al, 2007
30

80, F

?46,XX,i(17)(q10)(15)/46,X,i(X)(p10),i(17)(q10)(2)/46,XX(3)Adeyinka et al, 2007
31

84, F

?46,X,i(X)(p10)(14)/47,X,i(X)(p10),+8(2)/46,XX(2)Adeyinka et al, 2007
32

49, F

Thrombocytopenia46,X,i(X)(p10)(11)/46,XX(9) Adeyinka et al, 2007
33

76, F

Anemia46,X,i(X)(p10)(6)/46,XX(14) Adeyinka et al, 2007
34

79, F

Anemia, splenomegaly46,X,i(X)(p10)(16)/46,XX,t(9;12)(p23;q22)(3)/46,XX(2)Adeyinka et al, 2007

Prognosis

Survival was 8, 25 months (Dewald et al, 1989, cases # 15, #4) and 11+, 12+ months (Gindina, cases #25, #23 , table 1) in the four cases where information was provided.

Cytogenetics

Note

There is a problem of distinguishing i(X)(p10) from del(X)(q24) because of the similarity of X p-arm band pattern and X q-arm band pattern extending from the centromere to band Xq24.
Atlas Image
Figure 2. Partial karyotypes with extra i(X)(p10); Fluorescence in situ hybridization (FISH) with BreakApart CRLF2/Xp22.33 (CytoCell, UK) showing two normal X chromosomes and extra i(X)(p10) (4 fusion signals on interphase cells) in female patient with post-transplant relapse of ALL (Gindina, #23, table 1)

Probes

CRLF2 BreakApart (CytoCell, UK)

Additional anomalies

Sole abnormality in 11 patients, mostly in myeloid neoplasms (4 MDS, 3 AML, 2 CMML). Double extra i(X)(p10) was present in 4 patients (Selleri et al., 1989; Adeyinka et al., 2007; Hagemeier et al., 1981; Fitzerald et al., 1983). Additional chromosome anomalies were observed in 2/3 patients. Associated in combination with extra chromosome 8 in 5 females (Barbouti et al., 2002; Hagemeier et al., 1981; Dewald et al., 1989; Adeyinka et al., 2007), idic(X)(q13) in 2 (Dewald et al., 1989), del(20q) in 3 (Nacheva et al., 1995; Preiss et al., 2010; Falzetti et al., 1999), extra chromosome 20in 2 (Hagemeier et al., 1981;), loss of chromosome 7 in 2 (Lugthart et al., 2010; Schlegelberger et al. 1994), del(7q) in 2 (Falzetti et al., 1999; Schlegelberger et al. 1994), ring chromosome in 2 (Adeyinka et al., 2007; Temperani et al, 1995), other isochromosomes in 3 (Barbouti et al., 2002; Schlegelberger et al. 1994, Adeyinka et al., 2007).
In lymphoid malignancies, i(X)(p10) is part of a complex karyotype and seems to be a secondary event.

Result of the Chromosomal Anomaly

Oncogenesis

The pathogenetic importance of i(X)(p10) is underscored by its presence as the sole acquired anomaly. The major consequence of this abnormality is loss of the X q-arm and gain of the X p-arm, this would translate to loss of several genes on Xq and gain of several genes on Xp, that leads to genetic imbalance. I(X)(p10) has been reported in occasional males, indicating that this aberration can arise from active X chromosomes. It is not known whether this anomaly arises randomly from the active or inactive X chromosome in female patients (Adeyinka et al, 2007).

Bibliography

Pubmed IDLast YearTitleAuthors
179812112007Isochromosome (X)(p10) in hematologic disorders: FISH study of 14 new cases show three types of centromere signal patterns.Adeyinka A et al
145807752003A case of Down syndrome with acute lymphoblastic leukemia and isochromosome Xp.Baker JM et al
165737422006Prospective study of 174 de novo acute myelogenous leukemias according to the WHO classification: subtypes, cytogenetic features and FLT3 mutations.Bao L et al
122037762002Multicolor COBRA-FISH analysis of chronic myeloid leukemia reveals novel cryptic balanced translocations during disease progression.Barbouti A et al
196319822010Analyses on clinical characteristic and prognoses of 41 patients with chronic myelomonocytic leukemia in China.Chen B et al
27907521989Twenty-six patients with hematologic disorders and X chromosome abnormalities. Frequent idic(X)(q13) chromosomes and Xq13 anomalies associated with pathologic ringed sideroblasts.Dewald GW et al
101909421999Genomic instability and recurrent breakpoints are main cytogenetic findings in Hodgkin's disease.Falzetti D et al
65725481983Nonrandom cytogenetic changes in New Zealand patients with acute myeloid leukemia.Fitzgerald PH et al
69441531981Cytogenetic follow-up of patients with nonlymphocytic leukemia. II. Acute nonlymphocytic leukemia.Hagemeijer A et al
64903901984Chromosome instability is associated with hypodiploid clones in myelodysplastic syndromes.Knuutila S et al
206608332010Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia.Lugthart S et al
153345432004Structural integrity and expression of the L3MBTL gene in normal and malignant hematopoietic cells.MacGrogan D et al
77364431995Characterization of 20q deletions in patients with myeloproliferative disorders or myelodysplastic syndromes.Nacheva E et al
208758732010Cytogenetic findings in adult secondary acute myeloid leukemia (AML): frequency of favorable and adverse chromosomal aberrations do not differ from adult de novo AML.Preiss BS et al
119795522002t(1;3)(p36;p21) is a recurring therapy-related translocation.Sato Y et al
82895021994Cytogenetic findings and results of combined immunophenotyping and karyotyping in Hodgkin's disease.Schlegelberger B et al
27334551989Philadelphia-positive chronic myelogenous leukemia with typical bcr/abl molecular features and atypical, prolonged survival.Selleri L et al
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Summary

Atlas Image
Figure 1 Partial karyotype with extra i(X)(p10)

Citation

Tatiana Gindina

i(X)(p10) in female patients

Atlas Genet Cytogenet Oncol Haematol. 2016-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1500/i(x)(p10)-in-female-patients

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