Chronic granulocytic leukemia: Correlation of elastic transformation type with karyotypic evolution

Fm, O'Malley; Om, Garson

doi:10.1002/ajh.2830200402

Cited by 32 publications

(6 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conflicting results regarding their prognostic significance have been reported. Most authors have shown a definite correlation between additional abnormalities detected at the beginning of blast crisis and reduced survival [2,14,22,23,25,26], some did not find this association [1,6]. In our analysis, double Philadelphia chromosome and trisomy 8 were found to be associated with reduced survival in the univariate analysis; the latter retained prognostic significance in the multivariate analysis.…”

Section: Discussioncontrasting

confidence: 46%

Chronic myelogenous leukemia in blast crisis: retrospective analysis of prognostic factors in 90 patients

Grießhammer¹,

Heinze

Hellmann³

et al. 1996

Annals of Hematology

View full text Add to dashboard Cite

Ninety patients with Philadelphia chromosome-positive chronic myelogenous leukemia in blast crisis were reviewed to identify significant prognostic associations. At diagnosis of blast crisis the main clinical, laboratory, and cytogenetic data were recorded and evaluated for prognostic significance. At the time of the analysis 89 patients had died, with a median survival of 11 weeks from diagnosis of blast crisis. Patient characteristics demonstrated in the univariate analysis to have significant association with shorter survival were: thrombocythemia, leukocyte count above 20 x 10(9), Karnofsky index < 50%, nonlymphoid blast cell morphology, cytogenetic clonal evolution, the presence of a double Philadelphia chromosome or trisomy 8, and no response to therapy. In 17 of 59 patients (29%) evaluable for response to therapy a complete or partial remission was achieved. These responders had a significantly longer median survival (25 weeks) as compared with nonresponders (9 weeks). Response to therapy was significantly better in lymphoid blast crisis and in patients without clonal evolution. In a multivariate analysis containing all significant variables of the univariate analysis two parameters retained their prognostic significance: response to therapy and trisomy 8. In spite of the short overall survival in blast crisis, the determination of prognostic factors may be a useful tool for the clinician planning therapy, especially new therapeutic approaches.

show abstract

Section: Discussioncontrasting

confidence: 46%

Chronic myelogenous leukemia in blast crisis: retrospective analysis of prognostic factors in 90 patients

Grießhammer¹,

Heinze

Hellmann³

et al. 1996

Annals of Hematology

View full text Add to dashboard Cite

show abstract

“…23 Most authors have shown that the finding of additional changes is associated with reduced survival, but this is not universally agreed. [24][25][26][27][28][29] In this study approximately 65% of patients had additional cytogenetic changes and evidence of cytogenetic evolution was an independent adverse prognostic factor for survival. Its presence, however, had no impact on response to first therapy.…”

Section: Discussionmentioning

confidence: 56%

Factors affecting duration of survival after onset of blastic transformation of chronic myeloid leukemia

Wadhwa

Szydlo

Apperley

et al. 2002

Blood

View full text Add to dashboard Cite

“…It has been reported that additional abnormalities as such are more common in myeloid than in lymphoid BC and that +8, +19, and, in particular, i(17q) characterize myeloid BC, whereas monosomy 7 and various, atypical additional changes are typically found in lymphoid BC [53, 69, 175, 176, 177, 178, 179, 180, 181, 182]. However, some studies have failed to corroborate these associations [51, 52], and reviewing available literature data (table 4), the only significant differences in cytogenetic evolution patterns between myeloid and lymphoid BC are a higher incidence of i(17q) in myeloid BC and higher frequencies of monosomy 7 and hypodiploidy in lymphoid BC.…”

Section: Secondary Aberrations In Relation To Morphologymentioning

confidence: 99%

Cytogenetic and Molecular Genetic Evolution of Chronic Myeloid Leukemia

2002

View full text Add to dashboard Cite

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...

show abstract

Chronic granulocytic leukemia: Correlation of elastic transformation type with karyotypic evolution

Cited by 32 publications

References 21 publications

Chronic myelogenous leukemia in blast crisis: retrospective analysis of prognostic factors in 90 patients

Chronic myelogenous leukemia in blast crisis: retrospective analysis of prognostic factors in 90 patients

Factors affecting duration of survival after onset of blastic transformation of chronic myeloid leukemia

Cytogenetic and Molecular Genetic Evolution of Chronic Myeloid Leukemia

Contact Info

Product

Resources

About