+X solely in ALL

2017-07-01   Adriana Zamecnikova  

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

Abstract

Review on +X solely in acute lymphoblastic leukemia, with data on clinics.

Clinics and Pathology

Disease

Acute lymphoblastic leukemia (ALL), virtually all cases display a B-cell phenotype (except 1 T-cell ALL described by Heerema et al., 1998).

Epidemiology

34 patients (17 males and 17 females) aged 1 to 67 years (median 6 years); among them 17 patients were pediatric cases aged 1 to 16 years (median 4 years) (Privitera et al., 1992; Dastugue et al., 1992 ; Pui et al., 1993; Kempski et al., 1997; Heinonen et al., 1999; Silva et al., 2002; Chan et al., 2003; Kristensen et al., 2003; Russell et al., 2009; Lundin et al., 2014; Olsson et al., 2015; Liu et al., 2016). Up to half of these patients were Down syndrome (DS) cases (n=16) aged 1 to 13 years (Kalwinsky et al., 1990; Dastugue et al., 1992 ; Pui et al., 1993; Kempski et al., 1997; Heinonen et al., 1999; Mullighan et al., 2009; 2009; Russell et al., 2009; Lundin et al., 2014;). Adult patients were 20 to 59 years old (median 38 years) (from the known data) (Fuscaldo et al., 1981; Foa et al., 2003; Yamamoto et al., 2004; Chapiro et al., 2010; Eyre et al., 2012; Safavi et al., 2015; Yasuda et al., 2016) (Table 1).
Table 1. Clinical and karyotypic data of ALL patients with +X as a sole anomaly.
 Sex/AgeKaryotype
1 F/5947,XX,+X
2M48,XY,+X,+21c
3F/448,XX,+X,+21c
4M/7 47,XY,+X/47,idem,add(11)(p15)
5M/2 48,XY,+X,+21c
6F/448,XX,+X,+21c
7M46,XY,+X,inv(9)c      at relapse
8F/3 48,XX,+X,+21c
9M 47,XY,+X
10F/3 48,XX,+X,+21c
11F/16 47,XX,+X/47,idem,i(17)(q10)/47,idem,dup(1)(q21q32)
12F/16 47,XX,+X
13M/21 48,XY,del(1)(p22),t(1;19)(q23p13),+mar/47,XY,+X
14F/6 47,XX,+X
15F/53 47,XX,+X      at relapse
16M 48,XY,+X,+21c      PAR1 deletion, P2RY8-CRLF2 by RT-PCR
17M 48,XY,+X,+21c
18F 48,XX,+X,+21c
19F 48,XX,+X,+21c/48,idem,i(17)(q10)
20M 48,XY,+X,+21c
21M 48,XY,+X,+21c
22M 47,XY,+X
23M/4 48,XY,+X,+21c/49,idem,+17
24F/5 48,XX,+X,+21c
25F/3 47,XX,+X
26F/8 47,XX,+X
27F/38 47,XX,+X
28M/22 47,XY,+X      episomal amplification of NUP214-ABL1
29M/1348,XY,+X,+21c
30M/148,XY,+X,+21c
31F/2B47,XX,+X
32M/4147,XY,+X
33F/4 47,XX,+X
34M/20 47,XY,+X

Abbreviations: M, male; F, female
1. Fuscaldo et al., 1981; 2. Kalwinsky et al., 1990; 3. Dastugue et al., 1992; 4. Privitera et al., 1992; 5-6 Pui et al., 1993; 7. Chucrallah et al., 1995; 8. Kempski et al., 1997; 9. Heerema et al., 1998; 10. Heinonen et al., 1999; 11. Silva et al., 2002; 12. Chan et al., 2003; 13. Foa et al., 2003; 14. Kristensen et al., 2003; 15. Yamamoto et al., 2004; 16-22. Mullighan et al., 2009; 23-26. Russell et al., 2009; 27. Chapiro et al., 2010; 28. Eyre et al., 2012; 29-30. Lundin et al., 2014; 31. Olsson et al., 2015; 32. Safavi et al., 2015; 33. Liu et al., 2016; 34. Yasuda et al ., 2016.

Prognosis

+X as the sole anomaly may have not affect the prognosis in ALL patients and likely should be considered an indicator of low risk factor (Dastugue et al., 1992).

Result of the Chromosomal Anomaly

Oncogenesis

X-chromosome aneuploidy is a known numerical anomaly in ALL, especially in childhood ALL where it can be detected in nearly all children with a high hyperdiploid karyotype (Heinonen et al., 1999). It is also the most common acquired changes in DS-ALL were it is observed in between 25% and 50% of patients (Pui et al 1993). However, the acquired gain of an X chromosome as a sole abnormality has been observed only in a relatively small number of ALL patients. Notably, up to half of the cases were described in pediatric patients with Down syndrome, indicating that combination of trisomy 21 and +X chromosome seems to be typical of DS-ALL that and may lead to collaboration of genes on chromosomes 21 and X (Malinge et al., 2009). The result of chromosome X gain is an increased gene dosage that alters expression of many genes at the same time some of which could promote oncogenesis. In addition to an increased dosage of genes on chromosome X, recurring cryptic anomalies such as interstitial deletion of Xp22.33/Yp11.32 that juxtaposes the first, noncoding exon of P2RY8 (pseudoautosomal region 1 of chromosomes X and Y) with the coding region of CRLF2 (cytokine receptor-like factor 2) or translocations t(X;14) between these regions and the immunoglobulin heavy chain locus at 14q32.33 may contribute to leukemogenesis in B-cell acute lymphoblastic leukemia (Mullighan 2009; Russell et al., 2009).

Article Bibliography

Pubmed IDLast YearTitleAuthors
125379752003The spectrum of acute lymphoblastic leukemia with mature B-cell phenotype.Chan NP et al
204853702010A new recurrent translocation t(11;14)(q24;q32) involving IGH@ and miR-125b-1 in B-cell progenitor acute lymphoblastic leukemia.Chapiro E et al
86252241995Adult acute lymphoblastic leukemia at relapse. Cytogenetic, immunophenotypic, and molecular changes.Chucrallah AE et al
14584501992Prognostic significance of karyotype in a twelve-year follow-up in childhood acute lymphoblastic leukemia.Dastugue N et al
231756622012Episomal amplification of NUP214-ABL1 fusion gene in B-cell acute lymphoblastic leukemia.Eyre T et al
125809652003E2A-PBX1 fusion in adult acute lymphoblastic leukaemia: biological and clinical features.Foa R et al
67978811981Myeloproliferative disorders: III. CML: Further studies on the role of cytogenetics in diagnosis, prognosis and management.Fuscaldo KE et al
95520251998Frequency and clinical significance of cytogenetic abnormalities in pediatric T-lineage acute lymphoblastic leukemia: a report from the Children's Cancer Group.Heerema NA et al
102193381999Acquired X-chromosome aneuploidy in children with acute lymphoblastic leukemia.Heinonen K et al
21499601990Clinical and biological characteristics of acute lymphocytic leukemia in children with Down syndrome.Kalwinsky DK et al
93694341997Deletions of chromosome 21 restricted to the leukemic cells of children with Down syndrome and leukemia.Kempski HM et al
127560182003High-resolution comparative genomic hybridisation yields a high detection rate of chromosomal aberrations in childhood acute lymphoblastic leukaemia.Kristensen TD et al
274284282016Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia.Liu YF et al
247260342014Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries.Lundin C et al
191390782009Insights into the manifestations, outcomes, and mechanisms of leukemogenesis in Down syndrome.Malinge S et al
198381942009Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia.Mullighan CG et al
257270502015Cooperative genetic changes in pediatric B-cell precursor acute lymphoblastic leukemia with deletions or mutations of IKZF1.Olsson L et al
13484331992Different molecular consequences of the 1;19 chromosomal translocation in childhood B-cell precursor acute lymphoblastic leukemia.Privitera E et al
83154341993Immunophenotypes and karyotypes of leukemic cells in children with Down syndrome and acute lymphoblastic leukemia.Pui CH et al
196411902009Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia.Russell LJ et al
252610972015Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia.Safavi S et al
123932772002Cytogenetic analysis of 100 consecutive newly diagnosed cases of acute lymphoblastic leukemia in Rio de Janeiro.Silva ML et al
155718032004An extra X chromosome as a sole abnormality in relapse of an adult acute lymphoblastic leukemia.Yamamoto K et al
270191132016Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults.Yasuda T et al

Summary

Atlas Image
Figure 1. Fluorescence in situ hybridization with centromeric CEP X/Y probe (Abbott Molecular, Vysis, US) showing 2 copies of chromosome X (green signal) on metaphase and interphase cells. Partial karyotype showing an extra copy of chromosome X (inset).

Citation

Adriana Zamecnikova

+X solely in ALL

Atlas Genet Cytogenet Oncol Haematol. 2017-07-01

Online version: http://atlasgeneticsoncology.org/haematological/1799/deep-insight-explorer/favicon/css/lib/bootstrap.min.css