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Huh, Moon, and Chung: Incidence and Clinical Significance of Sex Chromosome Losses in Bone Marrow of Patients with Hematologic Diseases
Original Article

Korean J Leg Med 2007;27(1):56-61.

Published online: 10 February 2007

DOI: https://doi.org/10.3343/kjlm.2007.27.1.56

Incidence and Clinical Significance of Sex Chromosome Losses in Bone Marrow of Patients with Hematologic Diseases

Jungwon Huh, M.D., Heewon Moon, M.D., Wha Soon Chung, M.D.

Department of Laboratory Medicine, Ewha Womans University, College of Medicine, Seoul, Korea

Received 22 August 2006       Revised 19 October 2006       Accepted 31 October 2006

Copyright © 2007 The Korean Society for Legal Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Loss of sex chromosomes in bone marrow is observed both in elderly persons as an aging phenomenon and in patients with hematologic malignancies. The purpose of this study was to evaluate the incidence and clinical significance of sex chromosome losses in patients with hematologic diseases, comparing the characteristics between patients with sole and secondary sex chromosome losses in conjunction with other chromosomal abnormalities.

Methods

Study group included 868 patients with hematologic diseases between June 1998 and May 2006. The cells of bone marrow aspirates were processed using unstimulated culture methods such as direct, 24-hr and/or 48-hr culture. Sex chromosome losses were included in the karyotype, when X or Y chromosome loss is observed in more than 2 metaphase cells.

Results

The sex chromosome losses in bone marrow were found in 5.1% of the patients and 1.8% showed sex chromosome losses as a sole chromosomal abnormality. According to the disease categories, the incidences of sex chromosome losses were as follows: acute myelogenous leukemia (AML), 9.5%; acute lymphoblastic leukemia, 0%; myelodysplastic syndrome, 6.0%; chronic myelogenous leukemia 3.6%; myeloproliferative disorders, 1.3%; multiple myeloma (MM), 13.0%; chronic lymphocytic leukemia, 0%; malignant lymphoma, 3.8%; and benign hematologic diseases 2.2%. The patients with sex chromosome losses as a sole chromosomal abnormality were all male and median age was higher than that of patients with sex chromosome losses as a secondary abnormality (64 vs. 58 yr, P=0.02). The proportion of metaphase cells with sex chromosome losses was significantly lower in patients with sex chromosome losses as a sole chromosomal abnormality (40% vs. 100%, P<0.0001). The changes of sex chromosome loss were correlated with the disease status of AML and MM.

Conclusions

These results suggest that secondary sex chromosome losses in conjunction with other chromosomal abnormalities seem to be one of the clonal abnormalities, whereas sex chromosome losses as a sole change seem to be an aging phenomenon, but further studies are needed.

Keywords: Sex chromosome, Bone marrow, Aging, Clonal

References

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Table 1.
Incidence of sex chromosome losses at diagnosis or relapse of hematologic diseases
Disease Total N N (%) of sex chromosome losses
Sole Secondary
Overall 868 16 (1.8) 29 (3.3)
AML 168 1 (0.6) 15 (8.9)
ALL 79 0 (0.0) 0 (0.0)
CML 84 0 (0.0) 3 (3.6)
CLL 9 0 (0.0) 0 (0.0)
MDS 67 3 (4.5)* 1 (1.5)‖
MPD 80 1 (1.3)† 0 (0.0)
MM 78 2 (2.6) 8 (10.4)
Lymphoma 132 3 (2.3)‡ 2 (1.5)
Benign 271 6 (2.2)§ 0 (0.0)

* 2 refractory anemia, 1 refractory anemia with ringed sideroblast;

† 1 essential thrombocythemia; †No bone marrow involvement of lymphoma;

‡ 2 idiopathic thrombocytopenia, 1 chronic renal failure, 2 eosinophilia,

§ 1 reactive plasmocytosis;

‖ 1 refractory anemia.

Abbreviations: AML, acute myelogenous leukemia; ALL, acute lymphoblastic leukemia; CML, chronic myelogenous leukemia; CLL, chronic lymphocytic leukemia; MDS, myelodysplastic syndrome; MPD, myeloproliferative disorder; MM, multiple myeloma.

Table 2.
Comparison of characteristics between patients with sole and secondary sex chromosome losses
Characteristics Sex chromosome losses
Sole Secondary
Age (yr)* 64 (35–77) 58 (23–77)
Sex (M;F)' 16:0 16;13
Metaphase proportion with sex chromosome loss (%)†    
Overall 40 (15–95) 100 (13–100)
AML 85 100 (40–100)‡
CML − 100 (100)§
MDS 22 (20–30) 100‖
MPD 95 −
MM 44 (40–50) 82 (13–100)
Lymphoma 44 (20–55) 78 (60–95)**
Benign diseases 34 (15–55) −

* P=0.02;

† P<0.0001;

‡ 9 patients with t(8;21) and 6 with complex karyotype;

§ 3 patients with t(9;22);

‖ 1 patient with trisomy 8;

8 patients with complex karyotype;

** 2 patients with complex karyotype.

Abbreviations: See Table 1.

Table 3.
Follow up data of patients with sex chromosome losses
No. Case Age/Sex Diagnosis Date Loss (%) Karyotype
1 24/F AML 0 M 50 46,XX,t(8;21)(q22;q22)[7]/45,X,-X,t(8;21)(q22;q22)[10]/46,XX[3]
    CR 13 M 0 46,XX[20]
2 33/M AML 0 M 80 45,X,-Y,t(8;21)(q22;q22)[4]/46,XY[1]
    CR 8 M 0 46,XY[20]
3 54/M AML 0 M 100 45,X,-Y,t(8;21)(q22;q22)[20]
    CR 1 M 0 46,XY[20]
    CR 5 M 0 46,XY[20]
    Relapse 7 M 80 45,X-Y,t(8;21)(q22;q22)[12]/46,XY[3]
    CR 8 M 0 46,XY[17]
4 71/M AML 0 M 65 46,XY,t(8;21)(q22;q22)[6]/45,X,-Y,t(8;21)(q22;q22)[11]
    Persistent 2 M 100 45,X,-Y,t(8;21)(q22;q22)[9]
5 57/F AML 0 M 35 Complex karyotype with X loss[7]/46,XX[13]
    CR 3 M 0 46,XX[20]
    Relapse 7 M 5 Complex karyotype with X loss[1]/46,XX[19]
6 63/F AML 0 M 0 46,XX,add(11)(q23)[3]/46,XX,add(1)(p36.3)[2]/46,XX[25]
    Relapse 6 M 100 Complex and composite karyotype With X loss[20]
7 77/M AML 0 M 100 Complex karyotype with Y loss[6]
    Persistent 1 M 100 Complex karyotype with Y loss[16]
8 64/M AML 0 M 0 46,XY[6]
    CR 2 M 0 46,XY[20]
    Relapse 8 M 41 46,XY,add(1)(p36.3)[6]/45,X,-Y,add(1)(p36.3)[7]/46,XY[4]
    Persistent 9 M 100 45,X,-Y,add(1)(p36.3)[20]
9 59/M RA 0 M 15 45,X,-Y[3]/46,XY[17]
    RA 2 M 0 46,XY[12]
    RA 8 M 20 45,X,-Y[4]/46,XY[16]
10 37/F RCMD 0 M 100 46,X,-X,+8[6]/45,X,-X[3]
    RCMD 2 M 100 46,X,-X,+8[3]/45,X,-X[17]
11 70/M CML 0 M 100 45,X,-Y,t(9;22)(q34;q11.2)[20]
    CR 9 M 100 45,X,-Y[9]
    CR 15 M 95 45,X,-Y[19]/16,XY[1]
    CR 24 M 95 45,X,-Y[19]/16,XY[1]
12 65/F CML 0 M 100 45,X,-X,t(9;22)(q34;q11.2)[20]
      3 M 80 45,X,-X[16]/46,XX[4]
13 30/M CML 0 M 100 45,X,-Y,t(9;11;17;22)(q34;q13;q25;q11.2)[20]
    CR 18 M 0 46,XY[17]
    CR 52 M 0 46,XY[20]
14 52/F MM 0 M 100 Complex karyotype with X loss[9]
    CR 38 M 0 46,XX[20]
15 48/F MM 0 M 100 Complex karyotype with X loss[6]
    CR 14 M 0 46,XX[20]
    Relapse 20 M 41 Complex karyotype with X loss[7]/46,XX[10]
    Persistent 33 M 100 Complex karyotype with X loss[7]
16 47/F MM 0 M 82 Complex karyotype with X loss[9]/46,XX[2]
    CR 25 M 0 46,XX[20]
17 30/F MM 0 M 100 Complex karyotype with X loss[20]
    Persistent 1 M 17 Complex karyotype with X loss[1]/46,XX[5]
18 75/M Lymphoma 0 M 70 Complex karyotype with Y loss[14]/46,XY[6]
    persistent 1 M 100 Complex karyotype with Y loss[16]
19 35/M ITP 0 M 0 46,XY[20]
    ITP 14 M 15 45,X,-Y[3]/46,XY[17]

Abbreviations: M, months; CR, complete remission; AML, acute myelogenous leukemia; RA, refractory anemia; RCMD, refractory cytopenia with multi-lineage dysplasia; CML, chronic myelogenous leukemia; MM, multiple myeloma; ITP, idiopathic thrombocytopenic purpura.

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