i(8)(q10) in ALL
2017-06-01 Adriana Zamecnikova Affiliation1.Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait; [email protected]
Abstract
Isochromosomes are nonrandom chromosomal anomalies in acute lymphoblastic leukemia (ALL), but relatively few patients ALL and i(8)(q10) have been reported. In the majority of cases, i(8)(q10) was part of complex karyotypes, suggesting that it is a secondary chromosomal abnormality in ALL associated with clonal evolution.
Clinics and Pathology
Disease
Acute lymphoblastic leukemia
Phenotype stem cell origin
Associated with B-lineage immunophenotype with exception of 1 chronic myeloid leukaemia (CML) with lymphoid blast crisis of B-cell type who developed a secondary T-cell ALL (Dawson et al., 1999) case and 2 biphenotypic leukemia (Sulak et al.,1990; Saikevich et al., 1991) patients.
Epidemiology
At least 40 reported cases (21 males, 19 females aged 0 to 85 years; median age 17 years) were described. Nearly half the cases were children: 2 female infants (OMalley et al., 1988; Pui et al., 1991) and 12 pediatric cases aged 0 to 15 years (Pollak & Hagemeijer 1987; Krance et al., 1992; Pui et al., 1992; Rafi et al., 2000; An et al., 2008; Suenobu et al., 2010; Chapiro et al., 2011; Harrison et al., 2014; Olsson et al., 2015; Yasuda et al., 2016; Zhang et al., 2016) or young adults aged 17 to 24 years old ( Mossafa et al., 1994; Tang et al., 1998; Jarosova et al., 2000; Soriani et al., 2011; Harrison et al., 2014; Safavi et al., 2015) (Table 1).
1.Pollak & Hagemeijer 1987; 2.OMalley et al., 1988; 3.Sulak et al.,1990; 4.Kageyama et al., 1991; 5.Pui et al., 1991; 6.Saikevich et al., 1991; 7.Krance et al., 1992; 8.Pui et al., 1992; 9.Dewald et al., 1993; 10.Tuszynski et al., 1993; 11-13.Mossafa et al., 1994; 14.Pirc-Danoewinata et al., 1995; 15.Martineau et al., 1996; 16-17.Rieder et al., 1996; 18.Pabst et al., 1996; 19.Tang et al., 1998; 20.Dabaja et al., 1999; 21.Dawson et al., 1999; 22.Jarosova et al., 2000; 23.Rafi et al., 2000; 24.Rieder et al., 2003; 25.Strefford et al., 2007; 26-27.An et al., 2008; 28.Coyaud et al., 2010; 29.Kowalczyk et al., 2010; 30.Suenobu et al., 2010; 31.Soriani et al., 2011; 32.Chapiro et al., 2013; 33-36.Harrison et al., 2014; 37.Olsson et al., 2015; 38.Safavi et al., 2015; 39.Yasuda et al., 2016; 40.Zhang et al., 2016.
Abbreviations: M, male; F, female.
| Sex/Age | Karyotype | |
| 1 | F/7 | 47,XX,del(7)(p?),i(8)(q10),add(9)(p21),ins(9;9)(p21;q12q22),add(14)(q?) |
| 2 | F/0 | 46,XX,ins(11;4)/46,idem,del(5)(q15q33)/46,idem,del(5),i(8)(q10)/46,idem,t(2;4)(q33;p16),del(5)/47,idem,+8/ | 46,idem,t(9;10)(p13;q22) or t(9;10) (p22;q24)
| 3 | M/85 | 77-87,XY,-X,-Y,del(5)(q23)x2,i(8)(q10)x2,add(22)(q13),inc Bilineage or biphenotypic leukemia |
| 4 | M/53 | 46,XY,+1,der(1;16)(q10;p10),i(8)(q10),t(9;22),-12,der(15)t(12;15)(q12;p11),i(17)(q10),+21 |
| 5 | F/0 | 50,XX,+X,+X,i(8)(q10),+10,-20,+21,i(21)(q10)x2,+mar |
| 6 | M/63 | 43,XY,t(1;9)(q?32;p?24),-2,der(3)t(3;12;17)(p?14;p?11;q?25),-5,i(8)(q10),-12,der(17)t(3;12;17) Bilineage or biphenotypic leukemia |
| 7 | M/13 | 46,XY,i(8)(q10),t(12;17)(p13;q21) |
| 8 | M/10 | 46,XY,i(7)(q10),t(9;22)(q34;q11)/48,idem,i(8)(q10),+i(8)(q10)x2 |
| 9 | M | 49,XY,+4,+8,i(8)(q10)x2,t(9;22)(q34;q11),+der(22)t(9;22) |
| 10 | F | 46,XX,t(9;22)(q34;q11)/47,idem,+i(8)(q10)/47,idem,+8,i(8)(q10)x2 |
| 11 | F/60 | 46,XX,t(9;22)(q34;q11)/46,idem,i(8)(q10) |
| 12 | M/44 | 46,XY,i(8)(q10),t(9;22)(q34;q11) |
| 13 | F/24 | 46,XX,del(6)(q21q24),i(8)(q10) |
| 14 | M | 46,XY,t(14;18)(q32;q21)/46,XY,del(3)(p24),i(8)(q10),del(12)(p12) |
| 15 | F/42 | 47,XX,dup(1)(q21q32),add(2)(p11),+7,i(8)(q10),t(8;22)(q24;q11)/47,idem,-dup(1),+trp(1)(q21q32) |
| 16 | F/36 | 53,XX,+4,t(9;22)(q34;q11),i(8)(q10),+18,+19,+der(22)t(9;22)x2 |
| 17 | M/53 | 46,XY,t(9;22)(q34;q11)/45,XY,-7,i(8)(q10),ider(9)(q10)t(9;22),der(22)t(9;22) |
| 18 | M | 48,XY,i(8)(q10),t(9;22)(q34;q11),+2mar |
| 19 | F/21 | 46,XX,i(7)(q10),i(8)(q10),t(9;22) |
| 20 | M | 47,Y,-X,-5,-7,+13,-14,-15,+5-6mar/84-91,YY,-X,-X,-4,-4,-5,-5,-7,-7,i(8)(q10),-14,-14,-15,del(22)(q13),+8-10mar |
| 21 | M/39 | 46,Y,t(X;11),i(7)(q10),dup(8)(q21q22)/46,idem,i(8)(q10)/45,idem,-Y T-cell ALL after chemotherapy for CML |
| 22 | M/17 | 45,XY,i(8)(p?),?add(12),-21/45,XY,i(8)(q10),der(12)del(12)(p13)dic(12;21)(p13;p11) |
| 23 | F/15 | 45,X,-X,-6,del(7)(q21),i(8)(q10),-9,add(9),add(12)(q24),t(12;21)(p13;q22),der(13)t(?6;13)(q12;q32),der(22)t(9;22),+1-2mar |
| 24 | M/62 | 46,XY,del(1)(q32),i(8)(q10),-9,-10,der(22)t(9;22)(q34;q11),+2mar |
| 25 | F/48 | 45,X,-X,add(1)(p36),-5,add(6)(q15),i(8)(q10),add(18)(p11) |
| 26 | F/14 | 45,XX,i(8)(q10),dic(9;12)(p11;p11),der(17)t(?X;17)(?q12;?p11) |
| 27 | F/13 | 46,XX,dic(9;20)(p11;q11),+21/46,idem,i(8)(q10)/46,idem,add(15)(p10) |
| 28 | M/51 | 46,XY,i(8)(q10),t(9;22)(q34;q11),der(9)t(8;9)(q1?;p12) |
| 29 | M | 47,XY,i(8)(q10),+21c |
| 30 | F/13 | 45,XX,t(9;22)(q34;q11),add(10)(q22),-12,der(12)t(12;12)(p13;q13),i(17)(q10)/45,idem,i(8)(q10) 46,X,-X,+1,t(2;16)(p10;q10),+8,-9,t(9;22),add(10),-12,der(12),-13,i(17)(q10),+18,add(19)(p13),del(19)(q?),+21,-22,+mar/47,idem,+8 therapy for neuroblastoma |
| 31 | M/17 | 48,XY,i(8)(q10),+i(8)(q10)x2,t(9;22)(q34;q11)/49,idem,+der(22)t(9;22) |
| 32 | M/7 | 46,XY,t(14;20)(q32;q12)/46,idem,i(8)(q10) |
| 33 | F/7 | 45,XX,dup(1)(q21q32),i(8)(q10),t(9;14)(p22;q11),der(11)t(11;21)(q13;q11)t(21;22)(q22;q11)t(22;22)(q11;q22) |
| 34 | M | 46,XY,-21,+r/46,idem,inv(11)(p15q13)/46,idem,i(8)(q10) |
| 35 | F/19 | 44,XX,i(8)(q10),-10,add(11)(q23),add(12)(p13),-14,add(14)(q32),add(15)(q25), +16,add(21)(q22),-22,+mar |
Abbreviations: M, male; F, female.
Prognosis
As it occurs rarely as a sole anomaly only in sporadic cases in ALL, thus the prognosis is uncertain; patients with favorable primary aberrations and i(8)(q10) may maintain favorable clinical outcome similar to patients with +8; its combination with unfavorable primary anomaly or complex anomalies may lead to the worst prognosis.
Genes Involved and Proteins
Result of the Chromosomal Anomaly
Oncogenesis
Partial chromosome 8q gain resulting from an isochromosome i(8)(q10) is a nonrandom chromosomal anomaly in ALL. It occurs rarely as a sole anomaly and is mainly observed together with primary chromosome aberrations, most frequently with t(9;22)(q34;q11). Therefore, the occurrence of i(8)(q10) in ALL may signal clonal evolution, often associated with disease progression. The consequence of the formation of i(8)(q10) is gain of 8q and loss of 8p, leading to imbalances in gene dosage. As trisomy 8 is among the most common secondary chromosome changes in hematological malignancies, it is likely that gain of 8q, but not the loss of 8p is important in leukemogenesis. In this regard it is interesting to note, that while extra chromosome 8 is a common clonal evolution marker for progression in CML, the occurrence of i(8)(q10) has been only rarely described during CML transformation. While differential diagnosis between blast transformation of CML and Ph1(+) ALL may be difficult, particularly in cases identified initially in blastic crisis, it is possible that i(8)(q10) is a specific secondary anomaly to t(9;22)(q34;q11) in a pre-B immunophenotype ALL.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 18957548 | 2008 | Variable breakpoints target PAX5 in patients with dicentric chromosomes: a model for the basis of unbalanced translocations in cancer. | An Q et al |
| 23827691 | 2013 | Chromosomal translocations involving the IGH@ locus in B-cell precursor acute lymphoblastic leukemia: 29 new cases and a review of the literature. | Chapiro E et al |
| 20160164 | 2010 | Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study. | Coyaud E et al |
| 10360374 | 1999 | Deletions and losses in chromosomes 5 or 7 in adult acute lymphocytic leukemia: incidence, associations and implications. | Dabaja BS et al |
| 10444170 | 1999 | Secondary T-acute lymphoblastic leukaemia mimicking blast crisis in chronic myeloid leukaemia. | Dawson L et al |
| 8275455 | 1993 | The application of fluorescent in situ hybridization to detect Mbcr/abl fusion in variant Ph chromosomes in CML and ALL. | Dewald GW et al |
| 24166298 | 2014 | An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome. | Harrison CJ et al |
| 11156736 | 2000 | Importance of using comparative genomic hybridization to improve detection of chromosomal changes in childhood acute lymphoblastic leukemia. | Jarosová M et al |
| 1747460 | 1991 | Ph1-positive acute lymphoblastic leukemia associated with an isochromosome 17q. | Kageyama T et al |
| 20620600 | 2010 | Structural and numerical abnormalities resolved in one-step analysis: the most common chromosomal rearrangements detected by comparative genomic hybridization in childhood acute lymphoblastic leukemia. | Kowalczyk JR et al |
| 1534130 | 1992 | t(12;17)(p13;q21) in early pre-B acute lymphoid leukemia. | Krance RA et al |
| 8889503 | 1996 | Isochromosomes in acute lymphoblastic leukaemia: i(21q) is a significant finding. | Martineau M et al |
| 8174082 | 1994 | Isochromosome 8q: a new recurring secondary anomaly in adults with B-lineage acute lymphoid leukemia. | Mossafa H et al |
| 3258177 | 1988 | Acute lymphoblastic leukemia with a unique rearrangement between chromosomes 4 and 11. | O'Malley DP et al |
| 25727050 | 2015 | Cooperative genetic changes in pediatric B-cell precursor acute lymphoblastic leukemia with deletions or mutations of IKZF1. | Olsson L et al |
| 8704211 | 1996 | Frequent clonal loss of heterozygosity but scarcity of microsatellite instability at chromosomal breakpoint cluster regions in adult leukemias. | Pabst T et al |
| 7736430 | 1995 | Phorbol-12,13-dibutyrate improves the quality of cytogenetic preparation in lymphoid malignancies. | Pirc-Danoewinata H et al |
| 3312844 | 1987 | Abnormalities of the short arm of chromosome 9 with partial loss of material in hematological disorders. | Pollak C et al |
| 1571550 | 1992 | Isochromosomes in childhood acute lymphoblastic leukemia: a collaborative study of 83 cases. | Pui CH et al |
| 1878594 | 1991 | Characterization of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse. | Pui CH et al |
| 11129441 | 2000 | ETV6/CBFA2 fusions in childhood B-cell precursor acute lymphoblastic leukemia with myeloid markers. | Rafi SK et al |
| 14607762 | 2003 | Cell lineage assignment of cytogenetic findings in acute lymphoblastic leukemia using combined immunomagnetic cell separation and chromosome preparation. | Rieder H et al |
| 8982045 | 1996 | Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia. | Rieder H et al |
| 25261097 | 2015 | Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia. | Safavi S et al |
| 2033959 | 1991 | Multiparameter analysis of acute mixed lineage leukemia: correlation of a B/myeloid immunophenotype and immunoglobulin and T-cell receptor gene rearrangements with the presence of the Philadelphia chromosome translocation in acute leukemias with myeloid morphology. | Saikevych IA et al |
| 21767878 | 2011 | Three copies of isochromosome 8q in Ph+ B-cell acute lymphoblastic leukemia. | Soriani S et al |
| 17237825 | 2007 | Genome complexity in acute lymphoblastic leukemia is revealed by array-based comparative genomic hybridization. | Strefford JC et al |
| 20723114 | 2010 | Ph+ALL in a pediatric patient with neuroblastoma in infancy. | Suenobu S et al |
| 1694392 | 1990 | Biphenotypic acute leukemia in adults. | Sulak LE et al |
| 9615800 | 1998 | Frequent p53 mutation in relapsed acute lymphoblastic leukemia with cytogenetic instability: a longitudinal analysis. | Tang JL et al |
| 8412311 | 1993 | Detection and significance of bcr-abl mRNA transcripts and fusion proteins in Philadelphia-positive adult acute lymphoblastic leukemia. | Tuszynski A et al |
| 27019113 | 2016 | Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults. | Yasuda T et al |
| 27776115 | 2016 | Deregulation of DUX4 and ERG in acute lymphoblastic leukemia. | Zhang J et al |
Summary
Partial karyotypes with isochchromosome i(8)(q10) (A). Fluorescence in situ hybridization with LSI MYC probe hybridizing to 8q24 (Vysis/Abott Molecular, US) showing end-to-end joining of homologous chromosomes 8 at the telomeres (B). It can be hypothesized that telomeric fusion of homologous chromosomes can promote creation of an unstable dicentric chromosome potentially causing an unbalanced translocation product. However, the precise consequences of telomere fusion events and their role in formation of isochromosomes remain unclear.
Citation
Adriana Zamecnikova
i(8)(q10) in ALL
Atlas Genet Cytogenet Oncol Haematol. 2017-06-01
Online version: http://atlasgeneticsoncology.org/haematological/2052/i(8)(q10)-in-all
