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Results for “clonal evolution”

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PubMed2001

Competitive polymerase chain reaction as a method to detect the amplification of bcr-abl gene of chronic myeloid leukemia.

BACKGROUND AND OBJECTIVES: The chimeric product of the bcr-abl rearranged gene is critical in the pathogenesis of chronic myeloid leukemia (CML), yet its role in the progression of the disease remains unclear. There is some evidence that increased bcr-abl expression levels, possibly due to gene amplification, precede the clonal evolution of CML hematopoietic progenitors toward a fully transformed phenotype and might be involved in their resistance to interferon-alpha or tyrosine kinase inhibitors. DESIGN AND METHODS: To quantify the bcr-abl gene both at the genomic and at the transcriptional levels we developed a competitive polymerase chain reaction (PCR) strategy. The competitive PCR technique is based upon the co-amplification of the sample template (target) together with increasing amounts of a DNA fragment (competitor) sharing with the target the primer recognition sites, but differing in size. We constructed a competitor for the quantification of both b2a2 and b3a2 alternative splicing forms of the bcr-abl chimera and established the accuracy and reproducibility of our competitive strategy in a clone of the murine 32DG hematopoietic cell line (32D LG7), which bears a stable integration of a single copy of p210 bcr-abl fusion gene. We utilized this technique to follow, over a period of 200 days, the fusion gene copy numbers and transcription rates in several p210 bcr-abl-transduced 32D cell clones, an experimental condition mimicking the evolution of CML myeloid progenitors in vivo. RESULTS: Our results are consistent with p210 bcr-abl overexpression but not gene amplification associated with their clonal evolution. Increased p210 bcr-abl transcription rate is associated with the abrogation of radiation-induced apoptotic cell death, suggesting a role for the chimeric gene expression level in cell life expectancy after a genotoxic insult. INTERPRETATION AND CONCLUSIONS: We conclude that the assessment of gene amplification and expression might serve to improve prognostic classification and follow-up of CML patients.

Alternative Splicing↗

PubMed1983

The clinical and cytogenetic significance of C-banding on chromosome #9 in patients with Ph1-positive chronic myeloid leukemia.

The C-band polymorphism of chromosome #9 in 18 patients with chronic myeloid leukemia (CML) with a Philadelphia chromosome (Ph1) translocation between chromosomes #9 and #22 was examined using C- and Q-banding techniques on the same metaphases and the classification proposed by Patil and Lubs [1]. The C-band polymorphism of chromosome #9 in CML was found not to differ in leukemic cells with the Ph1 and phytohemagglutinin-stimulated lymphocytes without the Ph1 and to have a clonal origin, i.e., to arise from a single cell in which the Ph1 translocation has taken place. A comparison of the C-band polymorphism of chromosome #9, survival after diagnosis of the disease, and abnormal chromosomes in addition to the Ph1 indicates some interesting aspects. Patients with the smallest C-band (level 1) on chromosome #9 not involved in the Ph1 translocation and with a relatively large C-band (level 2) on chromosome #9 with the Ph1 translocation (C9-1,2) tend to have no clonal evolution and short survival after diagnosis of the disease. On the other hand, patients with other types of C-band patterns tend to have evidence of clonal evolution and long survival. This study suggests that the C-banding pattern in Ph1-positive CML might be utilized as a prognostic parameter in the disease and that the C-segment might have biological activity.

Adolescent↗

PubMed1992

Frequent clonal abnormalities of chromosome band 13q14 in B-cell chronic lymphocytic leukemia: multiple clones, subclones, and nonclonal alterations in 82 midwestern patients.

We performed cytogenetic analyses of peripheral blood lymphocytes from 82 Midwestern B-cell chronic lymphocytic leukemia (B-CLL) patients. The cells were cultured with mitogens for 3-4 days. At least 15 metaphase cells were analyzed in 79 (96%) cases. Fifty (63%) of the 79 patients had clonal chromosomal alterations. Structural modifications of the long arm of chromosome 13 at or near band 13q14 were the most frequent abnormalities, identified in 23 (46%) of the patients with clonal abnormalities. In several patients, the abnormality involving band 13q14 was the sole chromosomal alteration. There was a high incidence of complex karyotypes. Nine patients had multiple subclones that appeared to result from clonal evolution; seven patients had cytogenetically unrelated clones; three patients had both subclones and cytogenetically unrelated clones. Nonclonal abnormalities were also prominent. Our study confirms the high incidence of clonal abnormalities involving chromosome arm 13q and documents the clustering of abnormalities at band 13q14 in B-CLL. The evidence for clonal evolution and the presence of multiple unrelated clones in these patients suggest that B-CLL may not be a karyotypically stable disease.

Aged↗

PubMed1999

Clonal stability in children with acute lymphoblastic leukemia (ALL) who relapsed five or more years after diagnosis.

Although most relapses of childhood acute lymphoblastic leukemia (ALL) occur 24-36 months after first CR has been achieved, few patients relapse 5 or more years after CR achievement. The assessment of clonality has proved to be useful in determining whether even those very late events represent the reoccurrence of the original clone or alternatively a secondary leukemia. To gain further information on clonal stability in such late relapse, we performed detailed comparative Southern blotting and PCR analyses of TcRdelta and TcRgamma gene rearrangements in five ALL at presentation and subsequent relapse which occurred more than 5 years after diagnosis. At least one stable rearranged allele of the TcRdelta and TcRgamma loci was traced in all cases at presentation and clinical relapse despite a wide heterogeneity of the pattern of rearrangements. Our study extends to a larger series of patients previous findings which have sought to analyze the phenomenon of clonal evolution in children relapsed after more than 5 years of CCR. With respect to the potential pitfalls in monitoring minimal residual disease in childhood ALL for the presence of clonal evolution, our results highlight the combination of two target genes (such as TcRgamma and TcRdelta) as a tool to reduce false negative MRD results.

Blotting, Southern↗

PubMed1996

Clonality of basal cell carcinoma--molecular analysis of an interesting case.

Tumor cells represent a single clone of cells that have undergone a series of mutations in genomic DNA. This process, known as clonal evolution, is a distinguishing feature of cancer. The human androgen receptor gene (HUMARA; GenBank) contains a highly polymorphic cytosine-adenine-guanine trinucleotide repeat that can be used to determine clonality by depicting X chromosome inactivation patterns. Random X chromosome inactivation is consistent with polyclonality; nonrandom X chromosome inactivation indicates a clonal population of cells. Basal cell carcinoma (BCC) demonstrates an atypical growth pattern in that it grows slowly, rarely metastasizes, and is rarely lethal. Whether this tumor results from the accumulation of mutations in a single cell with subsequent clonal expansion or reflects a polyclonal response by a group of cells to a growth stimulus is unknown. To provide further insight into the molecular events characterizing BCCs, we determined the clonal origin of five modular BCCs from a female patient by analyzing X chromosome inactivation patterns at the HUMARA locus. All tumors demonstrated a nonrandom pattern of X chromosome inactivation, consistent with monoclonal proliferation. These findings provide strong genetic evidence that sporadic BCCs develop by clonal evolution and support the contention that a series of mutations in a single cell is responsible for the altered growth state seen in these transformed epithelial cells.

Aged↗

PubMed1993

The multiface morphology of acute leukemia.

Three distinct morphological phases during the course of acute leukemia in a 16 year old girl are described. The patient presented with morphology of acute lymphoblastic leukemia, relapsed with acute myeloblastic leukemia which later on evolved to monoblastic phase. This clinical, morphological and ultrastructural observation provides clinical evidence supporting the current concept of normal and leukemic haematopoiesis, as well as clonal evolution, according to which a stem cell is capable of giving rise to different haematopoietic lineages. It is conceivable that chemotherapy altered the balance between the stem cells and the bone marrow microenvironmental stromal cells, resulting in clonal evolution or release of a new subclone with the disease relapse.

Adolescent↗

PubMed1991

Translocations t(14;18) and t(8;14) with rearranged bcl-2 and c-myc in a case presenting as B-ALL (L3).

Follicular lymphoma is a low grade malignancy characterized by the translocation t(14;18), which involves the putative oncogene bcl-2. We describe a 73-year-old patient presenting with Burkitt acute lymphoblastic leukemia (B-ALL) L3 (Burkitt type), whose cells had the following immunophenotype: CD19+, CD22+, HLA-DR+, CD10+, TdT-, Cyt IgM-, CD34-. Analysis of 25 peripheral blood metaphases showed the presence of t(14;18) (q32;q21), and t(8;14) (q24;q32) in 24 cells and t(14;18) only in one cell, suggesting that the latter translocation came first during clonal evolution. Both bcl-2 and c-myc were rearranged in addition to the immunoglobulin heavy and light chain genes. The presence of small lymphoid cells in paratrabecular areas on the bone marrow biopsy, together with evidence of cytogenetic clonal evolution, was indicative of a transformation from a low grade follicular lymphoma to a more aggressive Burkitt type malignancy.

Aged↗

PubMed1998

Secondary abnormalities of chromosome 6q in B-cell chronic lymphocytic leukemia: a sequential study of karyotypic instability in 51 patients.

Although karyotypic abnormalities are well documented in B-cell chronic lymphocytic leukemia (B-CLL), few sequential cytogenetic studies have been done. In this study, peripheral blood lymphocytes from fifty-one patients with B-CLL were sequentially karyotyped over a mean interval of 13.8 months (range, one to 51 months). Cytogenetic clones were detected in 33/51 patients (66%) on initial study, including 17 patients with structural abnormalities of chromosome 13q14, and three patients with trisomy 12. Karyotypic evolution was documented in 22/51 patients (43%). The most common secondarily acquired chromosome aberrations were structural abnormalities of the long arm of chromosome 6 involving the region of 6q21-q24 (six patients). Four patients each had acquired structural abnormalities of 1q, 3p, 12q, and 13q. Disease progression, as measured by advance in Rai stage or death from the disease, was observed more often in the clonal evolution group than in the karyotypically stable group (11/22 vs. 5/29; P = 0.017). Patients with secondary abnormalities of 6q had a significantly decreased progression-free survival interval compared with other patients in the study (P = .023). The authors conclude that clonal karyotypic evolution is common in B-CLL, and that clonal evolution correlates with clinical disease progression. Furthermore, the poor outcomes previously attributed to CLL with 6q abnormalities may be related to the clonal acquisition of these abnormalities over time. Future studies should focus on the relevant genetic events underlying the clinical progression observed with karyotypic evolution of B-CLL.

Aged↗

PubMed1988

Cytogenetics of chronic myelogenous leukemia.

The fundamental pathogenetic significance of the Ph chromosome abnormality in CML has been clarified by molecular studies. However, this balanced reciprocal t(9;22) is probably not the primary event in the pathogenesis of this disease, at least at a cytogenetic level. The cause of Ph variants in +/- 5% of patients is still unknown. Improvements in cytogenetic techniques and molecular studies in a limited number of cases indicate that simple variants do not exist: Region 9q34 appears to be involved in all types of Ph variants. There is tentative evidence that these variants may in fact represent a clonal evolution from a standard t(9;22). The types of additional secondary abnormalities found in Ph variants are the same as those commonly found in standard cases. Ph negative CML represents a heterogeneous group of myeloproliferative/myelodysplastic disorders. The various mechanisms that could lead to Ph negativity are discussed. Some karyotypically normal cases and those showing a chromosome abnormality other than the Ph during the chronic phase have shown the same molecular changes as found in Ph positive CML. The types of clonal changes accompanying transformation to an acute phase are similar to those seen in myeloid disorders as a whole. The prognostic karyotypic factors in predicting imminent metamorphosis to the acute stage and during the acute phase are discussed. The extent of clonal evolution, the type of secondary abnormalities, and their relationship to the hematopoietic lineage of blast cells should be assessed. The nonrandom clonal changes found in 80% of cases are +Ph, +8, i(17q), +19, and loss of the Y. The significance of +Ph is possibly related to amplification of the bcr/abl fusion gene product, but the reason for the other persistent nonrandom changes is still speculative. Recent cytogenetic data indicate that the specific changes observed in various types of ANLL may be seen in corresponding types of MT, such as t(15;17) in promyelocytic transformations and abnormalities of 3q21-3q26 in megakaryoblastic transformations. Patients with LT usually have an early precursor B phenotype associated with a better prognosis. They tend to have either normal or hypodiploid karyotypes. An i(17q) is never seen and +8 and +19 are absent in most series. Duplication of the Ph and loss of the Y are common to both MT and LT. Data relating 14q+ abnormalities to LT are presently ambiguous.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromosome Aberrations↗

PubMed1992

Natural history of intraepithelial neoplasia in humans with implications for cancer chemoprevention strategy.

Intraepithelial neoplasia is of critical importance to the cancer chemoprevention field because it is a target condition for which drugs must be sought that will prevent its development or stop its progression. The term "dysplasia" refers to the morphological alterations that characterize intraepithelial neoplasia and according to many authors consists of seven basic morphological changes that occur in the majority of human epithelia, as well as in the epithelium of mouse skin papillomas induced by 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylphorbol-13-acetate: increased nuclear size; altered nuclear shape; increased nuclear stain uptake; nuclear pleomorphism (increased variation in nuclear size, shape, and stain uptake); increased mitoses; abnormal mitoses; and disordered or absent maturation. Clonal evolution appears to begin early in the neoplastic process during intraepithelial neoplasia. Aneuploidy has been found during intraepithelial neoplasia in many human epithelia, and, in association with other forms of genetic instability, may provide the increase in genetically variant cells required for clonal evolution to occur. It is postulated that two major factors affecting the rate of progression of intraepithelial neoplasia are the cellular mutation rate, which is enhanced by environmental carcinogens, and the cellular proliferation rate, which is enhanced by agents that include sex hormones, inducers of chronic inflammation, and irritant chemicals which stimulate reactive hyperproliferation. A preferred chemoprevention strategy should consist of the development of drugs and drug combinations which will block mutagenic carcinogens or prevent epithelial hyperproliferation or its causes. Two examples of the induction of regression of intraepithelial neoplasia by chemopreventive drugs are the regression of oral leukoplakia produced by beta-carotene and the regression of colorectal polyps in patients with familial polyposis produced by sulindac. It is evident that there is a strong need for more research on the induction of regression of intraepithelial neoplasia with chemopreventive agents. There is also a critical need to identify and develop biomarkers that correlate with the appearance and regression of intraepithelial neoplasia.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1987

Morphologic and phenotypic heterogeneity of two cases of translocation t(4;11) acute leukemia.

The morphological, ultrastructural, and immunological characteristics of two cases of acute leukemia with t(4;11) (q21;q23) were studied. The blasts from both cases were initially classified as L1 lymphoblasts. Ultrastructural examination indicated a heterogenous blast population in both cases, with some regular lymphoblast-like cells, and others exhibiting nuclear irregularity, small bundles of microfilaments, or large inclusions. In one case at diagnosis, fresh cells expressed B-associated and a myeloid antigen (B4 and 1G10). At the second relapse, the cells from this patient expressed another myeloid-associated antigen, LFA1 molecule, recognized by the monoclonal antibody M232 (CD18). At the end of clinical evolution, a further myeloid antigen was expressed (OKM1), while 8% peroxidase were noted. The other case was studied at diagnosis only and did not express any myeloid marker but expressed the B-associated B4 antigen. Furthermore, the case that exhibited a phenotypic transformation, was noted to show a chromosomal clonal evolution not described so far in other reported cases of t(4;11) acute leukemia. A dual lymphoid-myeloid nature of t(4;11) acute leukemia has been widely discussed. One of the cases reported here supports this hypothesis while the other does not. We would like to underline the possibility of heterogeneity of a case at presentation and transformation to a myeloid phenotype through clonal evolution.

Acute Disease↗

PubMed2001

Oligoclonal expansion of alphabeta T lymphocytes in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis with abnormal karyotypes.

We observed a fatal case of Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) with an abnormal karyotype. Increased levels of alphabeta T cells of the patient were investigated using an inverse polymerase chain reaction (PCR) of the T-cell receptor variable region gene, followed by Jbeta-PCR and single-strand conformation polymorphism (SSCP) to confirm the clonality of specific alphabeta-T cell subsets. A high frequency (>15%) was recognized in Vbeta9 at onset, but not in any Vbeta and Valpha families 2 weeks after chemotherapy. High levels (>20%) of some Jbeta genes were detected in all Vbeta families investigated, and the predominant bias of the Jbeta2 gene relative to the Jbeta1 gene (86.1% versus 13.9% at onset, and 77.4% versus 23.5% after chemotherapy) was recognized in pan-alphabeta T cells. When each Vbeta-Jbeta fragment was compared among the samples at onset and after chemotherapy by SSCP analysis, several distinct bands were observed that indicate a clonal evolution. Thus, the findings suggest that some of the alphabeta T cell clones could be associated with abnormal karyotypes in EBV-HLH. The present findings provide molecular evidence of the presence of oligoclonal T cells in pan-alphabeta-T cells and clonal evolution during a short clinical course in EBV-HLH with abnormal karyotypes.

Child↗

PubMed2003

Cytogenetic studies in patients on imatinib.

With the introduction of imatinib (Gleevec) (formerly STI571) for the treatment of chronic myeloid leukemia (CML), the various diagnostic methods used to monitor patients must be re-evaluated. Conventional cytogenetics has been the established method for follow-up of patients treated with interferon-alpha (IFN-alpha), and the prognostic value of major and complete cytogenetic remission was demonstrated in a number of studies. In patients on imatinib, these endpoints will likely remain valid, although longer observation is required. Cytogenetic remission as a time-dependent variable may aid risk stratification early on. Clonal evolution, ie, the presence of cytogenetic abnormalities in addition to the Philadelphia (Ph) chromosome, may provide important prognostic information as to the likely response to imatinib in all phases of CML but must be interpreted within the context of other disease characteristics. In some patients, clonal evolution is related to imatinib resistance. Information regarding the impact of specific types of additional cytogenetic abnormalities is still limited. Surprisingly, nonrandom karyotypic abnormalities have also been noted in the Ph-negative cells of some patients in cytogenetic remission. This is a novel phenomenon whose causality and prognostic implications require thorough and systematic evaluation.

Benzamides↗

PubMed2001

PCR techniques for clonality assays.

Clonal overgrowths represent the hallmark of neoplastic proliferations, and their demonstration has been proved useful clinically for the diagnosis of malignant lymphomas based on the detection of specific and dominant immunoglobulin and/or T-cell receptor gene rearrangements. Nonrandom genetic alterations can also be used to test clonal expansions and the clonal evolution of neoplasms, especially analyzing hypervariable deoxyribonucleic acid (DNA) regions from patients heterozygous for a given marker. These tests rely basically on the demonstration of loss of heterozygosity (LOH) resulting from either hemizygosity (nonrandom interstitial DNA deletions) or homozygosity of mutant alleles observed in neoplasms. LOH analyses identify clonal expansions of a tumor cell population, and point to monoclonal proliferation when multiple and consistent LOH are demonstrated. Based on the methylation-related inactivation of one X chromosome in female subjects, X-linked markers (e.g., androgen receptor gene) will provide clonality information using LOH analyses after DNA digestion with methylation-sensitive restriction endonucleases. Therefore, both non-X-linked and X-linked analyses give complementary information, related and not related to the malignant transformation pathway respectively. Applied appropriately, these tools can establish the clonal evolution of tumor cell populations (tumor heterogeneity), identify early relapses, distinguish recurrent tumors from other metachronic neoplasms, and differentiate field transformation from metastatic tumor growths in synchronic and histologically identical neoplasms.

Clone Cells↗

PubMed1978

Down's syndrome and leukemia: mechanism of additional chromosomal abnormalities.

There is an increased incidence of acute leukemia in patients with Down's syndrome patients have a trisomy-21 chromosomal pattern, and chromosomal abnormalities can be seen in acute leukemia. It is possible that the increased incidence of acute leukemia in Down's syndrome persons may be due in part to their chromosomal abnormalities. Such abnormalities, some appearing in a stepwise clonal evolution, were found in five Down's syndrome patients, four with acute leukemia and one with abnormal regulation of leukopoiesis. Morphological abnormal chromosomes were also found in three patients. These chromosomal abnormalities are similar to those seen in non-Down's syndrome leukemic patients. There is suggestive evidence for clonal evolution hypothesis of luekemogenesis in non-Down's syndrome patients. The abnormal chromosomal pattern reported in our Down's syndrome patients could be the result of nondisjunction in mitosis, and leukemia may be the phenotypical expression of this nondisjunction.

Acute Disease↗

PubMed2003

Comprehensive cytogenetic analysis including multicolor spectral karyotyping and interphase fluorescence in situ hybridization in lymphoma diagnosis. a summary of 154 cases.

Cytogenetic analysis including multicolor spectral karyotyping (SKY) and interphase fluorescence in situ hybridization (FISH) was performed on 154 consecutive cases with suspected lymphoma. The cytogenetic results were reviewed in correlation with the final pathologic diagnosis. A diagnosis of lymphoma was established in 94 cases, with 16 Hodgkin lymphomas and 78 non-Hodgkin lymphomas (NHL). Cytogenetic results were obtained in 63 NHLs (81%); 61 of those showed abnormal karyotypes (97%). The t(14;18) or IGH-BCL2 fusion was detected in 83% (20/24) of follicular lymphomas and in 57% (12/21) of diffuse large B-cell lymphomas (DLBCL). The application of interphase FISH and SKY has contributed to a high detection rate of t(14;18) in DLBCLs. This study showed that genes at 1q25, 3p21, 3q21, 5q31, 6p23, 7q22, 8q11 approximately q12, 9q34, 11q23, 12q13, and 19q13.1 may have been involved as the less common changes in follicular lymphoma and DLBCL. Comparison of the recurrent secondary aberrations in the groups of follicular lymphoma and DLBCL revealed a pattern of clonal evolution from the changes rea(1)(p36), del(6q), +7, +12 or dup or trp(12)(q13q22), +der(18)t(14;18), and +21 in follicular lymphoma to the changes rea(1)(p36), del(6q), +6, +7, +9, rea(11)(q23), +12, -13 or del(13(q12q14), +18, +21, and +X in DLBCL. The clonal evolution of the secondary aberrations is thought to contribute to the progression of the disease. About 90% (16/18) of other types of NHL had abnormal karyotypes showing specific translocations or gene rearrangements consistent with the pathologic diagnosis. A comprehensive cytogenetics approach including SKY and interphase FISH using probes for specific genes, such as IGH, BCL2, CCND1, and ALK, is a very useful ancillary diagnostic tool for lymphomas. The combined approach also led to the identification of t(2;19)(p23;q13.1) as a new variant of t(2;5)(p23;q35) in a case of Ki-1-positive anaplastic large cell lymphoma with a null cell phenotype.

Chromosome Aberrations↗

PubMed1986

Chromosomal aberrations in lymphocyte and fibroblast cultures of patients with the sporadic type of Kaposi sarcoma.

Numerical and structural chromosomal aberrations were found in metaphases from lymphocyte cultures from Sardinian patients with the sporadic type of Kaposi sarcoma, and also in fibroblasts derived from cultured biopsies of the tumoral lesions. In several cases there was evidence of clonal evolution of some of the chromosomal aberrations. The chromosomes most frequently involved in numerical aberrations were 10, 13, 15, 22 and the X and Y chromosomes, and those most frequently involved in translocations and deletions were 7, 13, 15, 22 and the X chromosomes. The hypothesis is made that in Kaposi sarcoma the chromosomal instability and clonal evolution in vivo could be modulated by the immunologic situation peculiar to the condition.

Aged↗

PubMed1996

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

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.

Adult↗