Structural rearrangements associated with the Ph1 chromosome in chronic granulocytic leukaemia

Potter, A. M.; Sharp, J. C.; Brown, M. J.; Sokol, Robert J.

doi:10.1007/bf00297627

Cited by 20 publications

(4 citation statements)

References 11 publications

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“…4 of t(4; 9;22) in Case 71 was different from those in the reported cases. The complex Ph 1 translocation, t(9;14;22), found in Case 72 and 3 reported cases (Potter et al, 1975;Borgstr6m, 1981;Shabtai et al, 1980) appeared to have the same break point at 14q24, whereas the break point in another reported case (Kolitz et al, 1981) of t(9;14;22) was located at 14q32.…”

Section: Discussionmentioning

confidence: 81%

Chromosome banding studies in 106 cases of chronic myelogenous leukemia

et al. 1982

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SummaryChromosome banding studies performed on 106 cases of CML in Sapporo revealed that 101 (95.3~) were Phi-positive, and 5 (4.7~) Phi-negative, the latter including a case of juvenile type CML. Of the 101 Phi-positive patients, 98 showed the standard type Ph ~ translocation, t(9;22)(q34;qll), while the remaining 3 had a complex Ph 1 translocation as represented by t(4;9;22), t(9;14;22), or t(9;10;15;19;22). There were 28 patients who showed otl~ler chromosome changes in addition to the Ph ~ translocation. Trisomy 8, duplication of Ph ~, isochromosome 17q, and trisomy 19 were most frequently involved in the additional changes, and 2 or more of them often participated in the major routes of karyotypic evolution. Other additional changes observed were 6 translocations, 4 partial deletions, 2 partial trisomies for lq, trisomies 6, 7, 12, 15, and 21, a monosomy 5, a partial duplication of no. 9, a missing Y, and so on.The present cytogenetic findings were evaluated with respect to some of the clinical and therapeutic parameters.

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Section: Discussionmentioning

confidence: 81%

Chromosome banding studies in 106 cases of chronic myelogenous leukemia

et al. 1982

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“…Harvesting and slide preparation w%ere the same as with marrow samples. (23,47 and 69) have been included in a previous publication (Potter et al, 1975). Two Phi cases (20%) showing deletion of Chromosome 22 were also found, and included with the non-standard Phl translocations in this study.…”

Section: Methodsmentioning

confidence: 99%

Significance of non-standard Philadelphia chromosomes in chronic granulocytic leukaemia

Potter¹,

Watmore²,

Cooke³

et al. 1981

Br J Cancer

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Summary.-One hundred and nineteen unselected and similarly treated patients with Ph1-positive chronic granulocytic leukaemia (CGL) had the precise nature of their chromosome rearrangements producing the Ph1 studied to determine whether this had any clinical relevance. Eighteen (15°,) did not have the usual 9/22 translocation and these, by life-table analysis, had a significantly shorter benign phase of their disease than the others (P<0.01). It further appeared that possession of a nonstandard Ph' was related to age, in that whereas only 24 patients were over 60 at diagnosis, 9 (33%) had a non-9/22 translocation (P<0.01).As the duration of the benign phase seemed to be shorter in those over 60 irrespective of Ph' type (P<0.01), the question arose whether non-standard PhI chromosomes were simply occurring in older patients or whether they were affecting prognosis independently. Their independent effect was suggested by the 11 patients under 60 with a non-9/22 Ph' who still had a significantly shorter benign phase than the 84 of similar age with a standard Ph' (P< 0.01). It is concluded that the myeloid karyotype can provide prognostic as well as diagnostic information in patients with CGL.

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“…Instead, either simple aberrations involving chromosome band 22q11 or complex changes affecting 9q34 and 22q11, and a third, or even a fourth and a fifth, chromosome were found [40, 41, 42, 43, 44, 45, 46, 47]. It was initially debated whether these variant rearrangements, found in 2–10% of larger series of Ph-positive CML [5, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61], had any specific phenotypic impact.…”

Section: Chromosome Banding Revealed Variant Translocations In CMLmentioning

confidence: 99%

Cytogenetic and Molecular Genetic Evolution of Chronic Myeloid Leukemia

2002

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Chronic myeloid leukemia (CML) is genetically characterized by the presence of the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL gene fusion on the derivative chromosome 22 called the Philadelphia (Ph) chromosome. In 2–10% of the cases, this chimeric gene is generated by variant rearrangements, involving 9q34, 22q11, and one or several other genomic regions. All chromosomes have been described as participating in these variants, but there is a marked breakpoint clustering to chromosome bands 1p36, 3p21, 5q13, 6p21, 9q22, 11q13, 12p13, 17p13, 17q21, 17q25, 19q13, 21q22, 22q12, and 22q13. Despite their genetically complex nature, available data indicate that variant rearrangements do not confer any specific phenotypic or prognostic impact as compared to CML with a standard Ph chromosome. In most instances, the t(9;22), or a variant thereof, is the sole chromosomal anomaly during the chronic phase (CP) of the disease, whereas additional genetic changes are demonstrable in 60–80% of cases in blast crisis (BC). The secondary chromosomal aberrations are clearly nonrandom, with the most common chromosomal abnormalities being +8 (34% of cases with additional changes), +Ph (30%), i(17q) (20%), +19 (13%), –Y (8% of males), +21 (7%), +17 (5%), and monosomy 7 (5%). We suggest that all these aberrations, occurring in >5% of CML with secondary changes, should be denoted major route abnormalities. Chromosome segments often involved in structural rearrangements include 1q, 3q21, 3q26, 7p, 9p, 11q23, 12p13, 13q11–14, 17p11, 17q10, 21q22, and 22q10. No clear-cut differences as regards type and prevalence of additional aberrations seem to exist between CML with standard t(9;22) and CML with variants, except for slightly lower frequencies of the most common changes in the latter group. The temporal order of the secondary changes varies, but the preferred pathway appears to start with i(17q), followed by +8 and +Ph, and then +19. Molecular genetic abnormalities preceding, or occurring during, BC include overexpression of the BCR/ABL transcript, upregulation of the EVI1 gene, increased telomerase activity, and mutations of the tumor suppressor genes RB1, TP53, and CDKN2A. The cytogenetic evolution patterns vary significantly in relation to treatment given during CP. For example, +8 is more common after busulfan than hydroxyurea therapy, and the secondary changes seen after interferon-alpha treatment or bone marrow transplantation are often unusual, seemingly random, and occasionally transient. Apart from the strong phenotypic impact of addition of acute myeloid leukemia/myelodysplasia-associated translocations and inversions, such as inv(3)(q21q26), t(3;21)(q26;q22), and t(15;17)(q22;q12–21), in CML BC, only a few significant differences between myeloid and lymphoid BC are discerned, with i(17q) and TP53 mutations being more common in myeloid BC and monosomy 7, hypodiploidy, and CDKN2A deletions being more frequent in lymphoid BC. The prognostic significance of the secondary genetic changes is not uniform, althoug...

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Structural rearrangements associated with the Ph1 chromosome in chronic granulocytic leukaemia

Cited by 20 publications

References 11 publications

Chromosome banding studies in 106 cases of chronic myelogenous leukemia

Chromosome banding studies in 106 cases of chronic myelogenous leukemia

Significance of non-standard Philadelphia chromosomes in chronic granulocytic leukaemia

Cytogenetic and Molecular Genetic Evolution of Chronic Myeloid Leukemia

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