Correlation between chromosomal abnormalities and blast phenotype in the blast crisis of Ph-positive CGL

Parreira, Leonor; Kearney, Lyndal; Rassool, F.; Babapulle, VB; Matutes, E.; Parreira, A; Castro, J. Tavares de; Goldman, J M; Catovsky, Daniel

doi:10.1016/0165-4608(86)90134-2

Cited by 50 publications

(21 citation statements)

References 15 publications

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“…The lymphoid-type transformation represented 32.2% (N = 29) of the total, a figure similar to those reported [4,5,13]. Of the patients tested, all were Ia and CD10 positive, with varying positivity for CD20 and CD19.…”

Section: Discussionsupporting

confidence: 66%

“…The reason why the chronic phase of CML transforms to a particular lineage of acute lymphocytic leukemia (ALL) is not known, but such transformations usually follow lines that are the normal developmental lines of the hematopoietic stem cell. Recent attempts have been made to correlate the additional cytogenetic changes that accompany or precede blast crisis with the lineage of the blast cells, but definitive patterns have not emerged [4,5].…”

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confidence: 99%

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Morphological and Immunological Pattern of Blastic Transformation in Chronic Myeloid Leukemia in Saudi Arabia: Study of 90 Transformations Among 248 Patients

et al. 1991

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We examined the pattern of blastic transformation in 90 of 248 patients (36%) with chronic myeloid leukemia who were seen at the King Faisal Specialist Hospital and Research Centre between 1975 and1988. The mean and median ages of all patients were 38.2 and 36.0 years, respectively. Four of the 90 transformants (4.4%) presented in blastic transformation, and 86 cases (95.5%) evolved from a well-defined chronic phase. Twenty-nine (32.2%) of the patients underwent lymphoid blastic transformation, while 28 (31.1%) were myeloid, seven (7.8%) were myelomonocytic, four (4.4%) were monocytic or erythroblastic, six (6.7%) were megakaryoblastic, ten (11.1%) were of mixed lineage, and two (2.2%) were unclassifiable. The lymphoid blast cells were uniformly common acute lymphocytic leukemia (i.e., Ia and CD10 positive), whereas the myeloid transformations were predominantly Ia negative. Mixed phenotype blasts were also predominantly Ia positive (i.e., 8 of 10), with varying positivity for CD10 and myeloid/monocytic markers. We conclude that blast crisis in chronic myeloid leukemia occurs in Saudi patients in a pattern similar to that seen in patients elsewhere, and that surface Ia antigen positivity in lymphoblast cells is a reliable marker for differentiating lymphoid from nonlymphoid crisis, in which the Ia antigen is not usually demonstrable.

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Section: Discussionsupporting

confidence: 66%

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confidence: 99%

Morphological and Immunological Pattern of Blastic Transformation in Chronic Myeloid Leukemia in Saudi Arabia: Study of 90 Transformations Among 248 Patients

et al. 1991

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“…T h e secondary anomalies are clearly nonrandom, the most frequent being trisomy 8, an isochromosome for the long arm of chromosome 17, trisomy 19, and an extra Ph chromosome (Mitelman, 1993). These secondary changes not only serve as valuable prognostic indicators in CML, but the type of additional aberrations also, albeit only to a lesser degree, seems to correlate with the phenotypic features of the ensuing acute leukemia (O'Malley and Garson, 1985;Parreira et al, 1986;Bernstein and Gale, 1990). Thus, the secondary anomalies are not merely indicative of genomic instability in the tumor cell population but are also most likely associated with the tumor phenotype and are of significance in the progression of the neoplasm, although no such causality has been proven.…”

Section: Evolution and Biologic Impact Of Neoplasia-associated Abnormmentioning

confidence: 95%

Primary vs. secondary neoplasia-associated chromosomal abnormalities—balanced rearrangements vs. genomic imbalances?

Johansson

Mertens

Mitelman

1996

Genes Chromosom. Cancer

155

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“…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

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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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Correlation between chromosomal abnormalities and blast phenotype in the blast crisis of Ph-positive CGL

Cited by 50 publications

References 15 publications

Morphological and Immunological Pattern of Blastic Transformation in Chronic Myeloid Leukemia in Saudi Arabia: Study of 90 Transformations Among 248 Patients

Morphological and Immunological Pattern of Blastic Transformation in Chronic Myeloid Leukemia in Saudi Arabia: Study of 90 Transformations Among 248 Patients

Primary vs. secondary neoplasia-associated chromosomal abnormalities—balanced rearrangements vs. genomic imbalances?

Cytogenetic and Molecular Genetic Evolution of Chronic Myeloid Leukemia

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