Significance of non-standard Philadelphia chromosomes in chronic granulocytic leukaemia

Potter, A. M.; Watmore, A. E.; Cooke, Patricia; Lilleyman, J S; Sokol, Robert J.

doi:10.1038/bjc.1981.146

Cited by 60 publications

(19 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data on the type and frequency of chromosome abnormalities in 106 cases of CML appeared to be somewhat different from those reported by the FIWCL (1978) and some other authors who studied relatively large numbers of CML cases (Lawler et al, 1976;Engel et al, 1977;Seabright and Pearson, 1978;Pasquali et al, 1979;Stoll and Oberling, 1979;Bernstein et al, 1980;Hagemeijer et al, 1980;Kohno and Sandberg, 1980;Sadamori et al, 1980;Fleischman et al, 1981;Potter et al, 1981 ;Oshimura et aI., 1982).…”

Section: Discussioncontrasting

confidence: 90%

“…Although the overall frequencies of both the standard and variant Ph 1 translocations and other types of chromosome abnormalities in CML have been estimated from time to time (LaMer, 1977;Sonta and Sandberg, 1977;FIWCL, 1978;Rowley, 1980;Sandberg, 1980;MiteIman and Levan, 1981), the number of cases dealt with in most of the reported series seems to be still insufficient to allow reasonable comparison of data among different geographic areas or ethnic groups. In fact, we are aware of only 5 original reports in which more than 100 cases of CML were investigated by banding methods (Seabright and Pearson, 1978;Pasquali et al, 1979;Fleischman et aL, 1981;Potter et aL, 1981;Oshimura et aL, 1982).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Chromosome banding studies in 106 cases of chronic myelogenous leukemia

et al. 1982

View full text Add to dashboard Cite

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.

show abstract

Section: Discussioncontrasting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Chromosome banding studies in 106 cases of chronic myelogenous leukemia

et al. 1982

View full text Add to dashboard Cite

show abstract

“…Two previous studies also noted a shorter survival in variant Ph-positive CML (Potter et al, 1981;Bernstein et al, 1984). Other groups, however, failed to support these findings (Sandberg, 1980;De Braekeleer, 1987).…”

Section: Discussioncontrasting

confidence: 38%

“…Previous survival analyses of variant Ph-positive CML, however, have yielded contradictory results. Several reports have noted a significantly worse prognosis in variant Ph-positive patients than in those with classical t(9;22) (Potter et al, 1981;Bernstein et al, 1984), however, other studies have failed to support this theory (Sandberg, 1980;De Braekeleer, 1987).…”

mentioning

confidence: 84%

Survival implications of molecular heterogeneity in variant Philadelphia‐positive chronic myeloid leukaemia

Reid¹,

Huntly²,

Grace³

et al. 2003

Br J Haematol

View full text Add to dashboard Cite

Summary. The BCR-ABL fusion in chronic myeloid leukaemia (CML) is generated by the Philadelphia (Ph) translocation t(9;22) or, in 10% of patients, variants thereof (vPh). Deletion encompassing the reciprocal product (ABL-BCR) from the derivative chromosome 9 [der(9)] occurs in 15% of all patients, but with greater frequency in vPh patients. Reports of physical separation of ABL-BCR in nondeleted patients, as well as evolution from classical to variant Ph, introduce further heterogeneity to the vPh subgroup and raise the possibility that such translocations may herald disease progression. Survival analyses, however, have thus far yielded contradictory results. We assessed the frequency of der(9) deletions, ABL-BCR abrogation, cytogenetic evolution and cryptic rearrangement in a large cohort of 54 patients with vPh CML. Deletions encompassing ABL-BCR were detected in 37% of patients, consistent with a model in which a greater number of chromosome breaks increases the risk of genomic loss. The components of ABL-BCR were physically separated in a further 52% of patients while fused in the remaining 11%. Evolution from classical to vPh was demonstrated in three patients. The difference in survival, as indicated by Kaplan-Meier analysis, was marked between classical and vPh patients (105 vs 60 months respectively; P ¼ 0AE0002). Importantly, this difference disappeared when patients with deletions were removed from the analysis. Our study showed that, despite the existence of several levels of genomic heterogeneity in variant Ph-positive CML, der(9) deletion status is the key prognostic factor.

show abstract

“…Second, a variant Ph chromosome was more frequent in patients with a deletion and, although controversial, some previous studies have suggested that such patients have a worse prognosis. 32,33 However this does not account for the survival difference reported here because there was no significant survival difference between patients with classical or variant Ph translocations (median survival 76 months versus 60 months, log-rank P ϭ .15). Moreover, analysis of the subgroup of 200 patients with classical Ph translocations revealed a worse survival for patients with a deletion compared to those without a deletion (median survival 38 versus 81 months, log-rank P ϭ .002).…”

Section: Deletion Status Is a Powerful Prognostic Indicator In CMLmentioning

confidence: 81%

Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia

Huntly

Reid²,

Bench³

et al. 2001

Blood

220

196

View full text Add to dashboard Cite

Chronic myeloid leukemia (CML) is characterized by formation of the BCR-ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. Large deletions on the derivative chromosome 9 have recently been reported, but it was unclear whether deletions arose during disease progression or at the time of the Ph translocation. Fluorescence in situ hybridization (FISH) analysis was used to assess the deletion status of 253 patients with CML. The strength of deletion status as a prognostic indicator was then compared to the Sokal and Hasford scoring systems. The frequency of deletions was similar at diagnosis and after disease progression but was significantly increased in patients with variant Ph translocations. In patients with a deletion, all Ph ؉ metaphases carried the deletion. The median survival of patients with and without deletions was 38 months and 88 months, respectively (P ‫؍‬ .0001). By contrast the survival difference between Sokal or Hasford high-risk and non-high-risk patients was of only borderline significance (P ‫؍‬ .057 and P ‫؍‬ .034). The results indicate that deletions occur at the time of the Ph translocation. An apparently simple reciprocal translocation may therefore result in considerable genetic heterogeneity ab initio, a concept that is likely to apply to other malignancies associated with translocations. Deletion status is also a powerful and independent prognostic factor for patients with CML. IntroductionChronic myeloid leukemia (CML) is a clonal hematologic malignancy that results from transformation of a multipotent hemopoietic stem cell. [1][2][3] The molecular hallmark of CML is the formation of a BCR-ABL fusion gene, usually formed as a consequence of the Philadelphia (Ph) translocation involving chromosomes 9 and 22. 4-6 BCR-ABL plays a pivotal role in the pathogenesis of CML and its formation is likely to represent the initiating event. In support of this concept transgenic and retroviral transduction studies have demonstrated that expression of BCR-ABL in murine bone marrow cells resulted in leukemia, with some cases closely resembling CML. [7][8][9][10][11][12][13] In one recent transgenic model the leukemia could be reversed by down-regulating BCR-ABL. 14 Chronic myeloid leukemia is a biphasic disease with an initial chronic phase that is readily controlled. However, this is followed by an ill-defined accelerated phase, and then a terminal blastic phase that resembles an acute leukemia, which is usually refractory to therapy. Transformation to blast crisis is accompanied by secondary cytogenetic changes in about 85% of cases, 15 but the molecular basis for this transformation is poorly understood. A number of molecular changes have been identified in a minority of cases of blast crisis, including mutations or deletions of p53, p16 INKA , and the retinoblastoma protein, and mutation or overexpression of Ras and EVI-1. 1,2 However, none provide a method for prospectively distinguishing those patients who will progress rapidly to blast...

show abstract

Significance of non-standard Philadelphia chromosomes in chronic granulocytic leukaemia

Cited by 60 publications

References 6 publications

Chromosome banding studies in 106 cases of chronic myelogenous leukemia

Chromosome banding studies in 106 cases of chronic myelogenous leukemia

Survival implications of molecular heterogeneity in variant Philadelphia‐positive chronic myeloid leukaemia

Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia

Contact Info

Product

Resources

About