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doi:10.1038/sj/leu/2401565

Cited by 5 publications

(2 citation statements)

References 237 publications

(257 reference statements)

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“…Signaling via RAS may be a central pathway in CML pathogenesis [129], but mutations involving the RAS gene family are very rare in CML [103, 106, 130, 131, 132, 133], although a possible association between the presence of RAS mutations and development of granulocytic sarcomas during BC has been suggested [134]. Recently, another ‘dominantly acting’ gene has received much attention in hematologic malignancies, namely CBFA2 .…”

Section: Molecular Genetic Changes Involved In CML Progressionmentioning

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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Section: Molecular Genetic Changes Involved In CML Progressionmentioning

confidence: 99%

Cytogenetic and Molecular Genetic Evolution of Chronic Myeloid Leukemia

2002

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“…Metaphases were G-banded by a trypsin-treated Giemsa stain and karyotyped according to the International System for Human Cytogenetic Nomenclature (ISCN 1995). FISH was carried out on the apheresis product using the –bcr/abl translocation DNA probe [13], and <5% of Ph+ cells were regarded as negative. A PCR technique was used to detect the presence of a fusion transcript form an abnormal BCR-ABL gene [14, 15].…”

Section: Methodsmentioning

confidence: 99%

Autologous Hematopoietic Stem Cell Transplantation in Chronic Myeloid Leukemia with Different Clinical Stages

Gopcsa¹,

Barta²,

Bányai³

et al. 2001

Acta Haematol

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Seven patients with Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) were treated with an ICE-based regimen plus G-CSF with the aim of mobilizing and collecting Ph-negative peripheral stem cells in the setting of an autologous transplant program. Five patients had CML in the first chronic phase and 2 in the accelerated phase. All patients had been previously treated with interferon-α. Median value and ranges for harvested mononuclear cells, CD34+ cells and CFU-GM, respectively: 5.65 × 10⁸/kg (2.61–11.38); 1.48 × 10⁶/kg (0.216–3.5), and 3.43 × 10⁴/kg (0.243–11.6). FISH was the only useful method for detection of minimal residual disease on apheresis product showing <5% t(9;22) positive cells in 2 cases and <10% positive cells in 4 other cases. Four of seven autologous grafts have been transplanted to date. Busulfan conditioning was used in 1 case and TBI/Cy conditioning in 3 other cases. All patients are alive and well following transplantation and are on interferon-α therapy.

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Myeloproliferative Erkrankungen

Hochhaus¹,

Niederle²,

Weidmann³

Therapiekonzepte Onkologie

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Cited by 5 publications

References 237 publications

Cytogenetic and Molecular Genetic Evolution of Chronic Myeloid Leukemia

Cytogenetic and Molecular Genetic Evolution of Chronic Myeloid Leukemia

Autologous Hematopoietic Stem Cell Transplantation in Chronic Myeloid Leukemia with Different Clinical Stages

Myeloproliferative Erkrankungen

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