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PubMed1996

Cytogenetic findings in 175 patients indicate that items of the Kiel classification should not be disregarded in the REAL classification of lymphoid neoplasms.

Cytogenetics have proved to be a valuable tool for classifying systemic lymphatic neoplasms, as this technique allows different stem line aberrations and clonal developments to be distinguished. This study was designed to analyze how far groups defined according to common cytogenetic features correlated with their position in either the Kiel (KC) or the REAL classification. Cytogenetic analyses were performed on material from 175 patients with lymphoid neoplasms (LN). Samples were prepared from peripheral blood and bone marrow in acute lymphoblastic leukemia (ALL), from bone marrow in multiple myeloma (MM), and from lymph node biopsies in lymphomas. The results of this study support the inclusion of ALL, MM, and extranodal lymphomas into a comprehensive classification, because their chromosomal aberrations were always characteristic for LN. From the cytogenetic point of view, a subgroup of ALL appears as a leukemic manifestation of lymphoblastic lymphoma. MM have structural aberrations of chromosomes 1, 11, and 14 and secondary aberrations of chromosomes 3, 6, 7, 12, 13, and 18, all of which are characteristic for lymphatic disease. The groups with follicle center cell lymphoma and mantle cell lymphoma correlate well with our results both in the low-grade subtype and in the blastic variant type, the majority of cases demonstrating t(14; 18) and its variants and t(11; 14), respectively. In contrast, the group of diffuse large B-cell (DLB) lymphomas proved to be heterogeneous on the basis of our cytogenetic results. Accordingly, we would suggest keeping the immunoblastic lymphoma (IB) subtype defined by the KC. IB demonstrates no stem line aberration in common with any other group and seems to be characterized by stem line aberrations involving chromosomes 3 and 6. As some DLB lymphomas have a t(14;18) or variant translocations involving chromosome 18, they should either be separated as a subgroup or included into the group of follicle center lymphomas.

Adult↗
PubMed1994

Cytogenetic studies, ras mutation, and clinical characteristics in primary myelodysplastic syndrome. A study on 68 Chinese patients in Taiwan.

Cytogenetics and clinical features were studied for 68 Chinese patients with primary myelodysplastic syndrome (MDS). Ras mutation was analyzed in 25 of them. Thirty-four patients (50%) had clonal chromosomal abnormalities at initial analysis. The most common cytogenetic aberrations were -7, +8, 5q-, and 20q-, which occurred in 11 (16.2%), seven (10.3%), five (7.4%) and three patients, respectively. The incidence of -7 was higher and that of 5q- lower in our patients than in patients from most other geographic areas. The 17 patients with multiple chromosomal abnormalities had a significantly shorter median survival (9 months) than the 34 patients with normal karyotype (33 months) and the 17 patients with patients with single anomalies (26 months). Evolution to acute leukemia occurred in 20 patients (29%) after a median interval of 8 months following the diagnosis. Patients with multiple cytogenetic changes at initial analysis or in subsequent studies had a significantly higher frequency of acute transformation than others (55% vs. 18.6%, p = 0.007); the same was not true if only the data of initial study were considered. Serial cytogenetic studies are important in patient follow-up. N-ras mutation was detected in 5 (20%) of 25 patients within the study. There was no correlation between the gene mutation and acute transformation. But combing the data of N-ras mutation and cytogenetics, patients with either the N-ras mutation or clonal chromosomal abnormalities were at significantly higher risk for developing acute leukemia than those with neither of the changes (77% vs. 25%).

Adolescent↗
PubMed1996

Detection of chromosomal abnormalities in uterine leiomyoma using conventional cytogenetic method and interphase fluorescence in situ hybridization.

Seventy-nine uterine leiomyomas were examined using a conventional cytogenetic method and fluorescence in situ hybridization (FISH) for detection of chromosomal abnormalities of chromosome 12. Nine (17.6%) of 51 tumor samples examined showed chromosomal abnormalities by conventional cytogenetic analysis. Rearrangements of chromosome 12 were detected in two tumors. Other tumors showed abnormalities affecting chromosomes 1, 4, 6, 7, 10, 13, 14, and 22. For FISH, the whole-chromosome painting probe and the D12Z3 probe specific for the centromeric region were used to detect structural and numerical abnormalities of chromosome 12. Of forty-one tumor samples, six showed structural aberrations and four showed numerical aberrations of chromosome 12 by FISH analysis. Of the tumors with structural aberrations identified by FISH, two had normal karyotypes, two showed structural rearrangements of chromosome 12 cytogenetically, and two could not be analyzed because of an insufficient number of metaphases. There were no correlations between the cytogenetic data and clinical parameters. The results indicate that chromosomal abnormalities are important in the biology of at least some types of uterine leiomyomas, and that FISH is a useful complement to conventional cytogenetic analysis in the study of solid tumors.

Adult↗
PubMed1996

Molecular remission achieved by interferon therapy in a patient with cytogenetically relapsed chronic myelogenous leukemia after syngeneic bone marrow transplantation.

A patient with chronic myelogenous leukemia (CML) in chronic phase (CP) had been treated with a syngeneic bone marrow transplantation (BMT). Cytogenetic remission was confirmed 3 months later. One year after transplantation, hematological remission persisted while cytogenetic analysis revealed a recurrence of Philadelphia chromosome (Ph1). Five months later, we began treatment with human lymphoblastoid interferon (HLBI), a natural interferon (IFN)-alpha. Fourteen months after initiation of HLBI administration, cytogenetic analysis of the patient's bone marrow showed disappearance of Ph1 positive cells. One year after confirming cytogenetic remission, the absence of bcr-abl transcripts by polymerase chain reaction (PCR) assay indicated molecular remission. IFN therapy appears to be the first choice of treatment for cytogenetic relapse after syngeneic BMT. The efficacy of IFN appears to be due to an anti-malignancy effect, not to graft versus leukemia (GVL) effect.

Adult↗
PubMed2004

Trisomy 4 as the sole cytogenetic abnormality in a patient with T-cell acute lymphoblastic leukemia.

Trisomies as sole cytogenetic abnormalities are extremely rare in acute lymphoblastic leukemia (ALL). We describe here the clinical features and immunophenotyping, cytogenetic, and fluorescence in situ hybridization (FISH) findings in a T-cell ALL patient with trisomy 4 as the sole cytogenetic abnormality. The leukemic clone was positive for CD2, CD7, CD34, and terminal deoxynucleotidyl transferase (TdT); CD13 was weakly expressed. Data on the tracking of the leukemic clone with immunophenotyping, cytogenetic, and FISH studies are discussed. The present case is compared with the three previous reported cases of trisomy 4 in ALL. Due to the rarity of this cytogenetic abnormality, its prognostic significance in ALL remains unclear.

Adolescent↗
PubMed2004

Cytogenetics and fluorescence in situ hybridization studies of diffuse large B-cell lymphoma in children and young adults.

Diffuse large B-cell lymphoma (DLBCL), the most common subtype of adult non-Hodgkin lymphoma (NHL), is infrequently seen in adolescents and is rare in children. Due to the infrequency of the disease, single institution-based cytogenetic and fluorescence in situ hybridization (FISH) studies of pediatric DLBCL have not been reported so far and, hence, the possible differences in pediatric and adult DLBCL have not been evaluated. We performed cytogenetic and FISH analyses of 7 pediatric and 5 young adult DLBCL cases referred to the University of Nebraska Medical Center. Karyotypic studies revealed numeric and structural chromosome abnormalities in all cases. Loss of chromosomes 2, 3, 4, 6, 12, 15, 16, and 17, and gain of 12, 18, and X were observed in more than 20% of the cases (#10878;3 cases). Sex chromosome abnormalities and cytogenetically unidentifiable chromosomes and/or segments were observed in 80% (10/12) of the cases. Recurrent breakpoints (observed in 3 or more cases) included 14q32 (IGH) and 17p13 (TP53), which clustered in the young adult group. The breakpoints 7q36, 9p24, 13q34, and 16q24 were noted in two cases each. We performed interphase FISH studies to verify the possible rearrangements of the breakpoints that are frequently implicated in adult DLBCL. Our results confirmed that the pediatric cases did not show rearrangements of 3q27 (BCL6), 14q32 (IGH), 18q21 (BCL2), 8q24 (CMYC), and 17p13 (TP53), except for one case with IGH;BCL2 dual fusion [t(14;18)(q32;q21)] and one with a 17p13 (TP53) deletion. Although 3q27 was noted to be rearranged by conventional cytogenetics in two young adult DLBCL cases, FISH investigations verified that BCL6 was not disrupted. The t(8;14)(q24;q32) with rearranged CMYC ascertained by FISH, was observed in a single young adult DLBCL case. These results highlight a distinctly different representation of cytogenetic abnormalities in pediatric versus adult DLBCL.

Adolescent↗
PubMed2006

Utility of interphase FISH to stratify patients into cytogenetic risk categories at diagnosis of AML in an Eastern Cooperative Oncology Group (ECOG) clinical trial (E1900).

We evaluated the efficacy of FISH to detect chromosome anomalies in the evaluation of young (<60 years) patients with AML. Patients were enrolled in E1900, an ECOG clinical trial for AML. The protocol was designed to collect bone marrow or blood for both cytogenetic and FISH studies at study entry (diagnosis). FISH for each patient was performed and utilized eight probe sets to detect t(8;21), t(9;22), t(11;var), t(15;17), inv(16), +8, -5/5q, and -7/7q. We analyzed 237 specimens with complete cytogenetic and FISH results. Results for each specimen were classified by probe set into one of six categories. The concordance rate between cytogenetic and FISH results ranged from 98 to 100% for all probe sets and kappa analysis for concordance had a p-value of <0.0001. The high level of agreement between cytogenetic and FISH results demonstrate the accuracy of a panel of eight FISH probe sets for the detection of significant abnormalities in AML. Data from this investigation support the use of FISH as an adjunct method to increase the yield of useful cytogenetic results in large cooperative trials and demonstrate the potential of FISH as a follow-up study of minimal residual disease in ECOG trials.

Acute Disease↗
PubMed1998

Success rate of cytogenetic analysis at the time of second-trimester dilation and evacuation.

OBJECTIVE: The aim of this study was to determine the success rate of cytogenetic analysis from specimens obtained at the time of second-trimester termination of pregnancy by dilation and evacuation. STUDY DESIGN: All second-trimester dilation and evacuations performed by a single practitioner at a single institution from 1993 through 1995 were evaluated to pick out those patients in whom biopsy specimens were submitted for cytogenetic analysis. The main outcome studied was the ability to obtain karyotype results for these specimens. RESULTS: Cytogenetic studies were performed on 258 dilation and evacuation specimens with a median gestational age of 18 weeks (range 13-25 weeks). The indications for termination were fetal aneuploidy (n = 88, 34%), sonographically diagnosed fetal malformations (n = 82, 32%), intrauterine fetal death (n = 67, 26%), oligohydramnios or premature rupture of membranes (n = 16, 6%), and others (hematologic and metabolic disorders, n = 5, 2%). Successful karyotyping was achieved for 99% of specimens obtained at second-trimester dilation and evacuation, with 3 failures of growth (1% failure rate). The failures included a 14-week molar pregnancy, an 18-week fetus with Dandy-Walker malformation, and a 19-week intrauterine fetal death. Of the samples obtained in cases of intrauterine fetal death, 99% (66/67) provided adequate cytogenetic information. CONCLUSIONS: Karyotyping for abnormal second-trimester pregnancies and intrauterine fetal deaths at the time of a dilation and evacuation procedure has a success rate nearing 100%. In contrast to previous reports, our data indicate that it is unnecessary to perform pretermination invasive karyotyping in patients with abnormal second-trimester pregnancies or intrauterine fetal death who elect to undergo dilation and evacuation. Chromosome analysis at the time of termination of pregnancy by dilation and evacuation reduces patient discomfort, risk of infection, and cost while still providing reliable and vital cytogenetic information for future genetic counseling.

Abortion, Induced↗
PubMed1999

Cytogenetic diagnosis of "normal 46,XX" karyotypes in spontaneous abortions frequently may be misleading.

OBJECTIVE: To use the molecular identification of Y chromosome material in products of conception cytogenetically diagnosed as "46,XX" to confirm the occurrence of inaccurate cytogenetic test results most likely attributable to maternal cell contamination. DESIGN: Retrospective analysis. SETTING: Academic medical center. PATIENT(S): Thirty-four archival tissues from cases of spontaneous abortion with a "46,XX" karyotype based on cytogenetic analysis. INTERVENTION(S): Maternal and villus DNA were extracted from microdissected, formalin-fixed, paraffin-embedded archival tissues. The presence of the X and Y chromosomes was detected with the use of polymerase chain reaction assays and confirmed with fluorescence in situ hybridization. MAIN OUTCOME MEASURE(S): Accuracy of cytogenetic evaluation of products of conception. RESULT(S): Four (29%) of 14 first trimester and 1 (5%) of 20 second trimester "46,XX" pregnancy losses contained Y chromosome-specific DNA and demonstrated a single X chromosome-specific allele by polymerase chain reaction analysis consistent with an "XY" karyotype. Fluorescence in situ hybridization was confirmatory in 4 of 5 samples that demonstrated single X and Y signals in villus cells. CONCLUSION(S): Inaccuracy exists in the cytogenetic analysis of early products of conception that most likely is due to maternal cell contamination. In the absence of confirmatory testing, such as with a "DNA fingerprinting" assay, reports of a "46,XX" karyotype should be used cautiously in patient counseling and management.

Abortion, Spontaneous↗
PubMed2003

Can amnio-polymerase chain reaction alone replace conventional cytogenetic study for women with positive biochemical screening for fetal Down syndrome?

To determine whether amnio-polymerase chain reaction (amnio-PCR) can replace conventional cytogenetic study for confirming the karyotype of fetuses in women with positive biochemical screening for fetal Down syndrome. To check the accuracy of this technique in our laboratory, we first compared the amnio-PCR results with those of conventional cytogenetic study in 235 patients referred from June 1999 to December 2001 for prenatal diagnosis in a referral center in Hong Kong. We then reviewed the results of 1526 amniotic fluid cultures performed for positive fetal Down syndrome screening between January 1997 and December 2001 and classified them as detectable or not detectable by amnio-PCR, using the assumption that we had replaced conventional cytogenetic study with amnio-PCR. The 235 amnio-PCR results were all informative, without a false-positive or false-negative result. Of the 1526 cases with positive fetal Down syndrome screening and no ultrasound abnormalities, only two cases of sex chromosome abnormalities and two cases of marker chromosomes would have been missed if conventional cytogenetic study had been replaced by amnio-PCR.Amnio-PCR can be an alternative to conventional cytogenetic study for women with positive biochemical screening for fetal Down syndrome and no demonstrable fetal structural abnormality.

Adult↗
PubMed2003

Value of combined morphologic, cytochemical, and immunophenotypic features in predicting recurrent cytogenetic abnormalities in acute myeloid leukemia.

To evaluate the reliability of previously described morphologic, cytochemical and immunophenotypic criteria for the identification of acute myeloid leukemias (AMLs) with t(8;21), inv(16)/t(16;16) and t(15;17), 300 cases were reviewed retrospectively. Eighteen AMLs with features of t(8;21), 31 with features of inv(16)/t(16;16), and 22 with features of t(15;17) were identified. Cytogenetic studies were available for 228 cases and identified 15 cases of t(8;21), 30 cases of inv(16)/t(16;16), 18 cases of t(15;17) and 11 cases 11q23 AML. The true positive rate for pre-cytogenetic evaluation was 95% for t(15;17), 88% for inv(16)/t(16;16) and 87.5% for t(8;21). No difference in 5-year survival was identified in the precytogenetic and corresponding cytogenetic disease groups. No specific features to predict 11q23 abnormalities were identified. This study confirms the reliability of a combined morphologic, cytochemical and immunophenotypic approach to the initial classification of AML. Cytogenetic studies are still needed on all cases to identify the small proportion of cases that will be missed by these methods and to identify other significant cytogenetic abnormalities in AML.

Acute Disease↗
PubMed1995

UK Medical Research Council randomised, multicentre trial of interferon-alpha n1 for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. The UK Medical Research Council's Working Parties for Therapeutic Trials in Adult Leukaemia.

Interferon-alpha may be better than cytotoxic drugs in the long-term management of patients with chronic myeloid leukaemia (CML) in chronic phase. To test this possibility 587 patients with CML in chronic phase were randomly allocated to receive lymphoblastoid cell-line interferon-alpha n1 (IFN-alpha, n = 293) or chemotherapy with busulphan or hydroxyurea (no IFN-alpha, n = 294) as maintenance after initial induction treatment with cytotoxic drugs. There was a significant survival benefit for patients in the IFN-alpha arm when analysed on the basis of intention to treat (2p = 0.0009). The median survival for those allocated IFN-alpha was 61 months and no IFN-alpha was 41 months. Out of 269 patients with Philadelphia-positive CML in the IFN-alpha arm with at least 6 months follow-up, 211 were evaluable for haematological response: 145 (68%) achieved good responses (A+ or A type), 37 (18%) had partial responses (B type) and 29 (14%) had poor responses (C type). Patients with types A and B responses had a better survival than those in the no IFN-alpha arm; patients with type C responses had survival equivalent to the no IFN-alpha arm. Of these 269 patients, 26 of whom had not started IFN-alpha, 59 (22%) achieved a significant degree of cytogenetic response but 210 (78%) did not have a response. Cytogenetic responders survived significantly longer than non-responders and even non-responders survived longer than patients in the no IFN-alpha arm. Since cytogenetic non-responders had worse than average prognostic features, they may also benefit from IFN-alpha therapy. We conclude that treatment with IFN-alpha prolongs the survival of patients with CML; benefits of IFN-alpha are not confined to cytogenetic responders but may extend to most, if not all patients receiving IFN-alpha treatment; and cytogenetic response to IFN-alpha treatment identifies patients with a relatively good prognosis.

Adult↗
PubMed1996

Interleukin-3 plus interleukin-6 may improve chromosomal analysis of multiple myeloma: cytologic and cytogenetic evidence in thirty-four patients.

To better define the role of interleukin-3 (IL-3) and IL-6 in the cytogenetic analysis of multiple myeloma (MM), we performed concomitant chromosome and cytologic studies in 34 patients. In each case, 10-30 x 10(6) bone marrow cells were incubated in two independent cultures consisting of conventional cytogenetic medium with and without IL-3 plus IL-6 added for 72 hours. 1-ml aliquots of each culture were aspirated at 24, 48, and 72 hours and exposed to colcemid for 6 hours. Cytospin preparations were then made and mitotic cells were counted and identified as plasma cells or as nonmalignant cells based on their reactivity with an appropriate anti kappa/lambda serum. Slides for conventional cytogenetic analysis were prepared at 72 hours. A greater than two-fold increase of mitotic plasma cells was observed in cytospin preparations from stimulated cultures versus unstimulated cultures in 15 of 34 cases, whereas a less than 2-fold increase, no variation or no mitosis was recorded in 19 cases. Comparison of the number of mitotic plasma cells in stimulated cultures at 24, 48, and 72 hours showed a decreased mitotic activity at 72 hours. Clonal abnormalities were detected by conventional cytogenetic analysis in 19 of 34 cases (55.8%). Recurrent clonal aberrations involved chromosome 13 (4 cases), chromosomes 1p, and 14q (3 cases); chromosomes 3p, 6q, 7q, and 9q (2 cases). We conclude that IL-3 + IL-6 may increase the number of dividing plasma cells in cytogenetic cultures and that a 2-day culture with these cytokines may facilitate the detection of chromosome abnormalities in MM.

Bone Marrow↗
PubMed1997

Cytogenetic aberrations and DNA ploidy in soft tissue sarcoma. A Southwest Oncology Group Study.

We performed cytogenetic analysis and determined DNA content by flow cytometry (FCM) on freshly disaggregated tumor biopsies from 45 patients with soft tissue sarcomas (STS). Cytogenetically aberrant clones characterized 30 (67%) tumors, with the remaining 15 yielding normal karyotypes with or without nonclonal aberrations. No tumors with multiple unrelated clones were observed. Among the 30 tumors with clonally abnormal karyotypes, 21 (70%) had near-diploid stemlines, six were near-triploid and three were near-tetraploid. Ten of the clonally aberrant tumors contained nonrandom chromosomal translocations characteristic of histologic subtypes. Overrepresentation of chromosomes 7 and 8 were common numerical aberrations. Structural aberrations most often involved chromosomes 1, 7, 9, 12, and 14. Clustering of breaks in 9p resulting in partial loss of the short arm was frequent. Unstable aberrations including rings, dicentrics, large markers, small numbers of double minutes, and telomeric associations were seen in nine tumors. With FCM, 27 (60%) tumors had aneuploid DNA content and 18 (40%) were DNA diploid. Of those 18 DNA diploid tumors, 11 showed clonal karyotypic aberrations. In addition, apparent discrepancies between the results of the cytogenetics and FCM with respect to ploidy pattern were seen in 13 samples; 11 had DNA content in the peritriploid to peritetraploid range but the corresponding karyotype was normal or near-diploid. When the findings of the cytogenetics and DNA content analyses were combined, an abnormal cell population by one or both methods was detected in 38 (84%) tumors. The concurrent application of standard cytogenetics and DNA ploidy by FCM provide complementary information confirming a high incidence of genetic alterations in STS.

Adolescent↗
PubMed2006

Local recurrence of myxofibrosarcoma is associated with increase in tumour grade and cytogenetic aberrations, suggesting a multistep tumour progression model.

Myxofibrosarcoma is one of the most frequent soft tissue tumours in elderly patients, mostly arising in the extremities. Grade I lesions are only locally aggressive whereas grade II and grade III lesions have metastatic potential. The differential diagnosis contains several other (benign) myxoid soft tissue tumours. A number of sarcomas are characterised by specific cytogenetic aberrations, giving not only insight in their biological pathways; they also serve as molecular markers in difficult diagnoses. Cytogenetic data on myxofibrosarcoma are scarce with only few isolated cases described in the literature. No specific chromosomal aberrations have been detected so far. Moreover, molecular pathways in tumorigenesis and progression of myxofibrosarcoma are barely understood. We studied the clinicopathologic data and karyotypes of 32 myxofibrosarcomas using conventional banding and multicolour COmbined Binary RAtio labelling fluorescence in situ hybridisation technique. We included eight grade I, eight grade II and 16 grade III lesions. In all, 22 were primary tumours, nine were local recurrences and one a lymph node metastasis. The myxofibrosarcomas showed equal sex distribution, were mostly located at the extremities with two thirds deep-seated and had an average age of occurrence of 66 years. We found normal karyotypes in eight cases and clonal beside nonclonal aberrations in 22 cases. Complex cytogenetic anomalies were found in all grades. However, no tumour-specific chromosomal abnormalities could be withdrawn. Local recurrences showed increase in grade compared to their primary lesions. Interestingly, these recurrences showed more complex cytogenetic aberrations. Increase in grade seems to parallel increase in cytogenetic aberrations and malignant potential. Since the chromosomal aberrations found were not tumour type specific, they seem to be rather the result of secondary events in tumour progression and tumour genetic instability. Based on these findings, we suggest that tumorigenesis of myxofibrosarcoma is mainly a multistep genetic process, probably ruled by genetic instability caused by targeted checkpoint genes.

Adult↗
PubMed1997

An extremely delayed cytogenetic response to interferon-alpha in a patient with chronic myeloid leukaemia.

In chronic myeloid leukaemia (CML), treatment with interferon alpha IFN-alpha results in loss of the Ph' chromosome in a significant proportion of patients. Most cytogenetic responses occur early at a median of 9 months after initiation of treatment and failure to detect a cytogenetic response within a predetermined period may be a reason for IFN-alpha withdrawal. We report a patient in whom IFN-alpha dosage was initially severely limited by bone marrow suppression but in whom continuing treatment led to a first cytogenetic response only after 53 months. Increasing Ph' negativity over a further 2 years was associated with improving haematological tolerance which permitted IFN-alpha dose escalation and complete cytogenetic remission was achieved at 7 years after diagnosis. This remission has been sustained and has thus followed the most delayed cytogenetic response to IFN-alpha so far reported.

Antineoplastic Agents↗
PubMed1997

Emergence of new clonal abnormalities following interferon-alpha induced complete cytogenetic response in patients with chronic myeloid leukemia: report of three cases.

New treatments which may change the course of a disease, or which have potential carcinogenicity, may result in the development of new cytogenetic or clinical disorders. Three patients with Philadelphia chromosome-positive (Ph-positive) chronic myeloid leukemia (CML) who developed new cytogenetic abnormalities after achieving a cytogenetic complete remission (CR) of their Ph-positive disease with interferon alpha (IFN-alpha) based therapy are described. Patient 1 developed chromosomal abnormalities involving chromosomes 5 (5q13-34) and later 7 (monosomy 7) 60 months after the start of therapy and 20 months after IFN-alpha was discontinued. A myelodysplastic syndrome was noted 83 months from the start of therapy. Patient 2 developed a myeloproliferative syndrome with 18p11 chromosomal abnormalities 90 months after the start of the therapy and 60 months after IFN-alpha was discontinued. Patient 3 developed a chromosome 11 abnormality (11q21-23) 23 months after the start of therapy, without hematological manifestations. All three patients remain in cytogenetic CR of Ph-positive disease with the hypermetaphase fluorescent in situ hybridization and polymerase chain reaction studies for BCR/ABL showing minimal residual disease. The emergence of new cytogenetic or clinical disorders in patients with CML on IFN-alpha therapy needs to be monitored. These findings may be related to changing the natural course of CML, to therapy, or to the emergence of suppressed clones in a stem cell disorder.

Aged↗
PubMed1997

Molecular cytogenetics of childhood hematological malignancies.

Cytogenetic and molecular analyses are essential for the classification of childhood hematologic malignancies. Nearly all children with leukemia should have an adequate cytogenetic analysis which in 80-90% is expected to show clonal chromosomal abnormalities. Moreover, with the availability of appropriate gene probes and sophisticated molecular techniques, genetic rearrangements become detectable in the majority of leukemia patients. Genetic abnormalities often associate with particular clinical-biological characteristics of the disease. In ALL, for example, genetic alterations together with distinct immunologic and clinical features, define various subgroups. In AML, unique cytogenetic rearrangements have been identified and associated with distinct morphological subgroups. Apart from the diagnostic assessment, cytogenetic studies provide valuable prognostic information which may influence treatment choices. Molecular analysis has also become of important value in the management of children with leukemias, as it serves, for example, to identify genetic abnormalities not detected by chromosomal analysis and to monitor residual disease during treatment and follow-up. Thus, genetic analyses of leukemic cells provide information of clinical relevance as well as contributing to our understanding of leukemogenesis. Alternative classifications of acute leukemias which take into account genetic information are being proposed. The available cytogenetic and molecular data have then to be included in clinical protocols, either by selecting individualized therapies in certain leukemia subtypes or by modifying treatment according to quantification of residual disease. We are closer to our main goal which is not only to classify 100% of childhood leukemias accurately, but to cure all of them.

Child↗