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PubMedDate not supplied

Pre-B acute lymphoblastic leukemia in a 3-year-old boy with pre-acute myelogenous leukemia myelodysplastic syndrome: cytogenetic evidence of common early progenitor cell ontogeny.

PURPOSE: Myelodysplastic syndromes in children commonly evolve into acute leukemia, usually acute myelogenous leukemia (AML) and rarely acute lymphoblastic leukemia (ALL). The lineage of the leukemia can be predicted based on characteristic morphologic and cytogenetic findings of the marrow and peripheral blood. PATIENT AND METHODS: A 3-year-old boy had refractory anemia with excess blasts and abnormalities suggestive of pre-AML with highly unusual cytogenetic changes. ALL of pre-B phenotype developed. RESULTS: Leukoerythroblastic anemia, pseudo Pelger-Huet neutrophils, and dysmyelopoietic hyperplasia of the marrow suggested likely early progression to AML. Complex cytogenetic abnormalities (monosomy 17 and 20, ring chromosome 11 with deletion of bands q23, and a derivative dicentric chromosome 12) were present in both the myelodysplastic marrow and the subsequent ALL. CONCLUSION: This case presents cytogenetic evidence of common early progenitor cell ontogeny of both malignancies (refractory anemia with excess blasts and ALL).

Anemia, Refractory, with Excess of Blasts↗
PubMed2006

High-resolution single-copy gene fluorescence in situ hybridization and its use in the construction of a cytogenetic map of maize chromosome 9.

High-resolution cytogenetic maps provide important biological information on genome organization and function, as they correlate genetic distance with cytological structures, and are an invaluable complement to physical sequence data. The most direct way to generate a cytogenetic map is to localize genetically mapped genes onto chromosomes by fluorescence in situ hybridization (FISH). Detection of single-copy genes on plant chromosomes has been difficult. In this study, we developed a squash FISH procedure allowing successful detection of single-copy genes on maize (Zea mays) pachytene chromosomes. Using this method, the shortest probe that can be detected is 3.1 kb, and two sequences separated by approximately 100 kb can be resolved. To show the robust nature of this protocol, we localized nine genetically mapped single-copy genes on chromosome 9 in one FISH experiment. Integration of existing information from genetic maps and the BAC contig-based physical map with the cytological structure of chromosome 9 provides a comprehensive cross-referenced cytogenetic map and shows the dramatic reduction of recombination in the pericentromeric heterochromatic region. To establish a feasible mapping system for maize, we also developed a probe cocktail for unambiguous identification of the 10 maize pachytene chromosomes. These results provide a starting point toward constructing a high-resolution integrated cytogenetic map of maize.

Chromosome Mapping↗
PubMed1985

The myelodysplastic syndromes: different evolution patterns based on sequential morphological and cytogenetic investigations.

Serial morphological and cytogenetic investigations were performed in 46 patients with the myelodysplastic syndrome (MDS). Twenty-one patients (45.5%) progressed to AML (greater than 30% blasts in bone marrow smears). Based on sequential determinations of percentages of bone marrow blasts, three patterns of evolution were observed in MDS. Patients with evolution pattern A (48%) had an apparently stable disease with minimal or no increase in bone marrow blasts. Exceptionally they developed new or additional chromosomal anomalies during the course of their disease. Cases in this group, who showed no abnormal localization of immature myeloid precursors (ALIP) at time of diagnosis experienced prolonged survival (median: 43 months), while ALIP positive patients had shorter survival times (median: 14 months), with high probability of early death from infections and/or bleeding problems. Patients with evolution pattern B (28%) initially had a morphologically stable disease, comparable to cases with evolution pattern A, but showed an abrupt shift from MDS to AML. Most of these patients (82%) were ALIP positive and a substantial proportion (46%) showed karyotype anomalies at diagnosis. The abrupt shift to AML in these patients was frequently (61.5%) associated with additional cytogenetic anomalies. Patients with evolution pattern C (24%) showed a gradual increase in bone marrow blasts. The majority of these cases (8/11) ultimately developed acute myeloid leukaemia (gradual progression to AML), whereas some patients (3/11) died from infections and/or haemorrhagic complications before they had reached the level of clinical AML. All of these patients were ALIP positive at diagnosis and no additional cytogenetic alterations occurred during evolution. Acquisition of new karyotypic anomalies during the course of MDS was almost invariably associated with abrupt shift to AML. From this retrospective study we conclude that evolution in MDS shows two important aspects, which seem to be preponderant in determining the course and outcome of the disease: one is the proliferative capacity and resulting growth advantage of the neoplastic clone over normal haematopoiesis, as measured by increasing percentages of bone marrow blasts in sequential aspirates; the other one is instability of the clone. Unstable clones have a high propensity to further intraclonal changes; they are expressed morphologically by the abrupt increase in bone marrow blasts and cytogenetically by the acquisition of new or additional karyotype anomalies.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Cytogenetics and their prognostic value in de novo acute myeloid leukaemia: a report on 283 cases.

Cytogenetic analysis was successfully performed at diagnosis in 283 patients with de novo acute myeloid leukaemia (AML), including eight children aged 6-15 and 275 adults. Mean age was 50.3 (range 6-86) and the M/F ratio was 1.23. 214 patients were treated by intensive chemotherapy and 75.2% achieved complete remission. Patients with inv(16) and t(8;21) had very high CR rates whereas those with complex cytogenetic abnormalities (with or without involvement of chromosomes 5 and/or 7) had a poor response to therapy. Other karyotypic abnormalities and normal karyotypes were associated with intermediate CR rates. In a multivariate analysis, cytogenetics were the best prognostic factor of the achievement of CR, followed by age and platelet count. Median actuarial disease-free survival (DFS) of the patients who achieved CR was 19 months. No significant differences in actuarial DFS were found according to karyotype. However, no relapses were seen in patients with inv(16) and t(9;11) or its variants. Conversely, the median DFS was only 12.5 months in patients with t(15;17). Median actuarial DFS was 24 months in patients with t(8;21), but a high incidence of early relapses were seen, and the actuarial DFS was only 54% at 12 months. Patients with trisomy 8 also had a median actuarial DFS of 24 months. Our findings do not support the previously reported 'favourable' prognosis of t(15;17) translocations. They suggest that, although it is characterized by a high CR rate, t(8;21) might be associated with a high incidence of early relapses and that, finally, inv(16) might be the only 'favourable' cytogenetic rearrangement in AML. Furthermore, the prognosis associated with t(9;11) or its variants (at least in adults), and trisomy 8 might be less severe than suggested in other studies.

Adolescent↗
PubMed1993

Improved cytogenetic analysis of bone marrow plasma cells after cytokine stimulation in multiple myeloma: a report on 46 patients.

Cytogenetic analysis was successfully performed in 46 consecutive myeloma patients (40 newly diagnosed and six relapsed patients). Karyotype was performed on bone marrow cells after long-term cultures (6 d) stimulated by GM-CSF, GM-CSF+IL6 or GM-CSF+IL6+IL3. Nineteen patients (41%) had cytogenetic abnormalities including 17/40 patients at diagnosis (42.5%) and 2/6 patients at relapse. Hyperdiploidy was found in 12 patients and hypodiploidy in four patients. Of the 17 newly diagnosed patients with cytogenetic abnormalities, five died from myeloma after 1-14 months and three other patients had primary drug resistance. Our results suggest that cytogenetic analysis after stimulation of cultures by cytokines detects clonal abnormalities in 40-50% of newly diagnosed myeloma patients and that these patients often have a short survival and/or primary drug resistance.

Bone Marrow↗
PubMed1992

Collecting duct carcinoma: cytogenetic characterization.

Most renal cell carcinomas are assigned to either the papillary or clear cell, non-papillary type by morphological and cytogenetic criteria. In rare cases, papillary carcinomas of the kidney have been classified as collecting duct carcinoma because of their medullary localization and the associated hyperplastic and dysplastic epithelial lesions of collecting ducts in the vicinity of the tumour. In this first report on the cytogenetics of collecting duct carcinoma, we describe unique and consistent chromosomal aberrations in three cases. Each of the three tumours showed monosomies for chromosomes 1, 6, 14, 15, and 22. This suggests that collecting duct carcinoma is the third type of kidney tumour whose definition is based on morphological as well as on cytogenetic criteria. It appears to be cytogenetically different from the cortical papillary kidney tumour which exhibits trisomy 17 and tri- or tetrasomy 7, and from the non-papillary renal cell carcinoma which characteristically presents deletion of the short arm of chromosome 3.

Adult↗
PubMed1994

Merkel cell carcinoma. Histopathology, immunohistochemistry, and cytogenetic analysis.

BACKGROUND: Merkel cell carcinoma (MCC) is a cutaneous neoplasm, histopathologically difficult to differentiate from other small blue cell neoplasms. Immunohistochemical and ultrastructural analyses are usually helpful in differentiating these neoplasms. Recently, cytogenetic analysis has emerged as a potential tool in the diagnosis of solid neoplasms, including MCC. OBJECTIVE: To describe the immunohistochemical and cytogenetic features of a case of primary MCC and to review the cytogenetics literature on MCC. METHODS: Formalin-fixed tissue was processed routinely and labeled with a battery of antibodies. Metaphase cells from fresh tissue were prepared by Giemsa banding. RESULTS: Histopathologically, there were irregular aggregates of pyknotic cells with little cytoplasm. Immunohistochemically, the neoplastic cells stained positive for neurofilament, cytokeratin, neuron-specific enolase, and epithelial membrane antigen. Leucocyte common antigen, S-100, 013, and chromogranin were negative. Karyotyping of neoplastic cells showed loss of chromosome Y (-Y). CONCLUSIONS: Coexpression of cytokeratin and neurofilament is characteristic of MCC and allows it to be differentiated from similar neoplasms. The significance of Y chromosome loss is unclear. Further cytogenetic analyses are warranted to identify genetic mutations significant to the pathogenesis of MCC.

Aged↗
PubMed2004

Robust classification of renal cell carcinoma based on gene expression data and predicted cytogenetic profiles.

Renal cell carcinoma (RCC) is a heterogeneous disease that includes several histologically distinct subtypes. The most common RCC subtypes are clear cell, papillary, and chromophobe, and recent gene expression profiling studies suggest that classification of RCC based on transcriptional signatures could be beneficial. Traditionally, however, patterns of chromosomal alterations have been used to assist in the molecular classification of RCC. The purpose of this study was to determine whether it was possible to develop a classification model for the three major RCC subtypes that utilizes gene expression profiles as the bases for both molecular genetic and cytogenetic classification. Gene expression profiles were first used to build an expression-based RCC classifier. The RCC gene expression profiles were then examined for the presence of regional gene expression biases. Regional expression biases are genetic intervals that contain a disproportionate number of genes that are coordinately up- or down-regulated. The presence of a regional gene expression bias often indicates the presence of a chromosomal abnormality. In this study, we demonstrate an expression-based classifier can distinguish between the three most common RCC subtypes in 99% of cases (n = 73). We also demonstrate that detection of regional expression biases accurately identifies cytogenetic features common to RCC. Additionally, the in silico-derived cytogenetic profiles could be used to classify 81% of cases. Taken together, these data demonstrate that it is possible to construct a robust classification model for RCC using both transcriptional and cytogenetic features derived from a gene expression profile.

Carcinoma, Renal Cell↗
PubMed2004

Tumor-associated endothelial cells with cytogenetic abnormalities.

Tumor angiogenesis is necessary for solid tumor progression and metastasis. Tumor blood vessels have been shown to differ from normal counterparts, for example, by changes in morphology. An important concept in tumor angiogenesis is that tumor endothelial cells are assumed to be genetically normal, although these endothelial cells are structurally and functionally abnormal. However, we hypothesized that given the phenotypic differences between tumor and normal blood vessels, there may be genotypic alterations as well. Mouse endothelial cells were isolated from two different human tumor xenografts, melanoma and liposarcoma, and from two normal endothelial cell counterparts, skin and adipose. Tumor-associated endothelial cells expressed typical endothelial cell markers, such as CD31. They had relatively large, heterogeneous nuclei. Unexpectedly, tumor endothelial cells were cytogenetically abnormal. Fluorescence in situ hybridization (FISH) analysis showed that freshly isolated uncultured tumor endothelial cells were aneuploid and had abnormal multiple centrosomes. The degree of aneuploidy was exacerbated by passage in culture. Multicolor FISH indicated that the structural chromosomal aberrations in tumor endothelial cells were heterogeneous, indicating that the cytogenetic alterations were not clonal. There was no evidence of human tumor-derived chromosomal material in the mouse tumor endothelial cells. In marked contrast, freshly isolated normal skin and adipose endothelial cells were diploid, had normal centrosomes, and remained cytogenetically stable in culture even up to 20 passages. FISH analysis of tumor sections also showed endothelial cell aneuploidy. We conclude that tumor endothelial cells can acquire cytogenetic abnormalities while in the tumor microenvironment.

Aneuploidy↗
PubMed2005

Effects of chemotherapy on the cytogenetic constitution of Wilms' tumor.

The management of Wilms' tumors consists of a combination of surgery, chemotherapy, and possibly radiotherapy. To date, chemotherapy is being risk stratified according to histologic subtype and stage. Although the cytogenetic characteristics of Wilms' tumors are well established, the cytogenetic effects related to chemotherapy are widely unknown. We herein report on comparative genomic hybridization findings in 41 primary Wilms' tumors of blastemal type, of which 19 had received preoperative chemotherapy (PCT group) and 22 did not (non-PCT group). Overall, imbalances could be detected in 32 tumors, with +1q (17 cases), +7q (10 cases), +7p (6 cases), and -7p (6 cases) as the most common changes. Among these, +7q and -7p were both significantly associated with metastatic disease at the time of surgery (P = 0.002 and 0.007, respectively), and +7q was also associated with higher stage (stages III + IV; P = 0.003). There were significant differences in the cytogenetic constitution of tumors between the two treatment groups. As a trend, tumors in the preoperative-chemotherapy group had fewer changes (mean, 2.7) than those in the non-preoperative-chemotherapy group (mean, 3.8), and the frequencies of imbalances at 7p or +7q, respectively, were significantly lower compared with tumors in the non-preoperative-chemotherapy group (2 of 19 versus 10 of 22, P = 0.019; 1 of 19 versus 9 of 22, P = 0.011). In contrast, -1q was common in both the preop-CT group (10 of 19) and the non-preop-CT group (7 of 22). The results suggest that Wilms' tumor clones with +1q are not obliterated by preoperative chemotherapy, whereas cytogenetically more complex clones with +7q and/or imbalances at 7p seem more responsive and are more likely to be eliminated by chemotherapeutic treatment.

Adolescent↗
PubMedDate not supplied

Diagnosis of small non-cleaved cell lymphoma by fine needle aspiration utilizing cytomorphologic features combined with cytogenetic analysis.

OBJECTIVE: To determine the utility of cytogenetic studies in the diagnosis of small non-cleaved cell lymphoma by fine needle aspiration. STUDY DESIGN: Cases of suspected lymphoma were identified in a prospective fashion by an immediate examination of the fine needle aspirate material by the pathologist. In these instances, additional material was aspirated directly into RPMI 1640 medium for cytogenetic studies. RESULTS: Four cases of suspected small non-cleaved cell lymphoma were identified on fine needle aspirate material, and the diagnosis was confirmed in all cases by the presence of the characteristic (8;14) translocation or associated variant translocation in cytogenetic studies from the aspirated material. CONCLUSION: Cytogenetic analysis is useful as an additional ancillary technique applicable to fine needle aspiration material. In the case of suspected small non-cleaved cell lymphoma, the finding of a translocation (8;14) or associated variant translocation, along with the characteristic cytomorphology, allows a definitive diagnosis by fine needle aspiration and may alleviate the need for biopsy.

Aged↗
PubMed1991

Cytogenetic and flow cytometric DNA analysis in renal cell carcinoma.

Cytogenetic and flow cytometric DNA analyses were performed on 37 tumor samples from 16 patients with renal cell carcinoma. 36 cultures were chromosomally abnormal and 1 was normal. The most frequent abnormality was trisomy or tetrasomy of chromosome 7 (13 of 16 tumors), suggesting that this abnormality might be a primary change in renal cell carcinoma. Abnormalities of chromosome 3 were seen in 9 of 16 tumors (56%). Eight of 11 tumors (73%) with cytogenetic results from multiple tumor samples showed intratumor cytogenetic heterogeneity. Twelve of the 16 patients had aneuploid tumors, and 4 had homogeneously diploid tumors. DNA index correlated with chromosome number. No association was found between cytogenetic results and clinical stage.

Aneuploidy↗
PubMed1980

DNA content analysis by flow cytometry and cytogenetic analysis in mycosis fungoides and Sézary syndrome.

Flow cytometric (FCM) analysis of DNA content was performed on 82 lymph node and peripheral blood specimens from 46 patients with mycosis fungoides and the Sézary syndrome. Overall, 32 of the 46 patients (70%) had aneuploidy detected by FCM. Aneuploidy was present in 63% of the patients at the time of diagnosis before systemic therapy. In these patients, aneuploidy was frequently detected in blood and lymph node specimens scored as negative by cytology and histology, suggesting that unsuspected extracutaneous dissemination is present in many patients at the time of diagnosis. Direct comparison with Giemsa-banded cytogenetic studies showed an excellent correlation of FCM results and cytogenetic chromosome number. However, FCM frequently detected a larger fraction of aneuploid cells, and mitogen-stimulation studies suggest this is the result of preferential stimulation of normal lymphocytes by phytohemagglutinin. Thus, mitogens with a preference for malignant T cells, such as staphylococcal protein A, should be used for cytogenetic analysis of malignant T-cell disorders. At diagnosis, some histologically positive specimens contained only diploid cells by FCM and cytogenetic analysis. These patients had a more indolent clinical course than patients with aneuploidy. Aneuploidy was detected by FCM as either wide G(1) or as discrete aneuploid peaks. The presence of aneuploidy at any time in the clinical course implied a poor prognosis. Discrete hyperdiploid peaks were associated with large cell histology, early relapse, and aggressive clinical course. The development of hyperdiploidy at relapse was documented in four patients and was associated with a transition to large cell histology and a poor prognosis. Similar studies may elucidate differences in natural history and mechanism for transition in histology in other lymphomas and solid tumors.

Chromosome Banding↗
PubMed1991

Cytogenetic and molecular genetic studies of follicular and papillary thyroid cancers.

Cytogenetic studies have shown frequent clonal abnormalities in papillary carcinoma (PTC) and follicular carcinoma (FTC). Loss of heterozygosity (LOH) may suggest the presence of tumor suppressor genes and has not been reported in these neoplasms. These studies were undertaken to determine if consistent chromosomal abnormalities are associated with thyroid cancer, to determine likely regions for molecular genetic investigations, and to determine if there is allelic loss in thyroid tumors. Cytogenetic analysis of 26 PTC and 5 FTC showed clonal abnormalities in 9 and included -Y, +5, or inv(10)(q11.2q21.2) in PTC, and -Y or near haploidy in FTC. Using DNA probes specific for chromosomes 1, 3, 10, 16, and 17, we carried out restriction fragment length polymorphism analysis on 6 FTC, 3 follicular adenomas (FA), and 12 PTC. LOH of all informative loci on chromosome 3p was observed in all 6 FTC, but not in FA or PTC. No LOH was observed for loci mapped to chromosome 10 in PTC. Our results suggest: cytogenetic abnormalities of chromosome 10q are associated with PTC; cytogenetic and molecular abnormalities of chromosome 3 are associated with FTC; and a tumor suppressor gene may be present on the short arm of chromosome 3 important for the development or progression of FTC.

Adenocarcinoma↗
PubMed1997

Cytogenetic and Molecular Evaluation in Myelodysplastic Syndrome and in Acute and Chronic Leukemia.

BACKGROUND: The majority of the presently known nonrandom chromosome changes in hematologic malignancy were described during the 1970s and 1980s. The last 10 years have been devoted to the location of oncogenes and tumor suppressor genes altered as a consequence of those changes. New molecular methodology has helped speed this process, which has resulted in DNA sequencing of many of the genes involved, permitting molecular detection of abnormal clones. METHODS: This review examines the most common alteration-based subgroups of cytogenetics and molecular genetics in hematologic disorders with the exclusion of lymphoma. Prognosis has been updated to reflect improving treatment protocols. RESULTS: The versatility of cytogenetics for delineating genetic changes is difficult to match by molecular testing. Once a clonal anomaly is identified, molecular methodology can detect residual disease with far greater sensitivity than cytogenetics, but relies on translocation junction targets that exclude clones characterized by deletion or trisomy. CONCLUSIONS: Cytogenetic and molecular testing offers independent diagnostic and prognostic evaluation for most patients with hematologic malignancy.

Journal Article↗
PubMed2002

Vitamin E protection from/potentiation of the cytogenetic toxicity of cisplatin in Swiss mice.

Possible protection from or potentiation of the cytogenetic toxic effects of cisplatin (CP) 5 mg/kg b.w. in mouse bone marrow, spermatogonia by three different doses of alpha-tocopheryl acetate (vitamin E) 100, 200 and 300 mg/kg, and the transmission of such effects in the male germline, were assessed. CP-induced chromosomal aberrations (CAs) in bone marrow were decreased in vitamin E pretreated mice, but significantly (P < or = 0.05) only with vitamin E 300 mg/kg. The percentages of dividing cells in bone marrow were increased in vitamin E-pretreated groups of mice, but not significantly. However, the frequency of CP-induced micronuclei (MN) in polychromatic erythrocytes (PCEs) declined significantly (P < or = 0.01) in all the vitamin E-pretreated groups of mice. In spermatogonia the CP-induced CAs were also decreased significantly by vitamin E 200 mg/kg (P < or = 0.01), and 100 and 300 mg/kg (P < or = 0.05). However, transmission of CP-induced cytogenetic toxic effects from spermatogonia to spermatocyte, resulting in the formation of aberrant primary spermatocytes, was enhanced significantly in the mice pretreated with vitamin E 100 mg/kg (P < or = 0.05) and 200 mg/kg (P < or = 0.01). But the enhancement in the transmission of such effects was not significant in the mice pretreated with vitamin E 300 mg/kg. Besides, there was no significant change in vitamin E-pretreated groups of mice in the transmission of cytogenetic toxicity of CP from spermatogonia to sperm with the manifestation of abnormal sperm morphology. Thus, vitamin E protected bone marrow and spermatogonia from the cytogenetic toxic effects of CP, particularly efficiently at the highest tested dose (300 mg/kg), but it failed to protect from the transmission of such effects in the male germline of mouse and rather potentiated them to some extent. Treatment with vitamin E, an antioxidant, might be capable of protecting noncancerous cells from the oxidative damage caused by cisplatin but it might also reduce the effects of cisplatin on cancerous cells. Thus, the benefits of antioxidant treatment during cancer chemotherapy is yet to be demonstrated clearly.

Animals↗
PubMed2003

Acquired FANCA dysfunction and cytogenetic instability in adult acute myelogenous leukemia.

Myelodysplastic and leukemic stem cell clones that evolve in children and adults with Fanconi anemia universally bear complex cytogenetic abnormalities. The abnormalities are generally recurring deletions or chromosomal loss and involve precisely the same chromosomes with the same frequency as has been described in marrow cells from patients with secondary acute leukemia induced by alkylating agents. Reasoning that acquired Fanconi anemia protein dysfunction might contribute to cytogenetic instability in secondary acute myelogenous leukemia (AML) cells, we analyzed leukemic cells bearing characteristic complex cytogenetic defects obtained from a 68-year-old man whose lymphoblasts showed no evidence of Fanconi anemia. Unlike the lymphoblasts, this myeloid leukemia cell line (UoC-M1) was hypersensitive to mitomycin-C (MMC) and diepoxybutane (DEB) and exhibited a marked decrease in nuclear FANCA, FANCG, and FANCD2-L. Retroviral transduction of FANCA significantly reduced MMC sensitivity but FANCF, FANCG, and FANCC did not. Overexpression of FANCA restored levels of both FANCA and FANCG, whereas overexpression of FANCG or FANCC did not restore FANCA levels. The molecular mass of cytoplasmic FANCA, FANCG, FANCC, and nuclear FANCD2 were normal. All exons of FANCA and FANCG were sequenced, and no mutations were found. We conclude that perturbations of as yet unidentified factors that govern the binding activity or intracellular localization of FANCA may promote cytogenetic instability and clonal progression in patients with AML who do not have Fanconi anemia.

Aged↗
PubMed2003

BAALC expression predicts clinical outcome of de novo acute myeloid leukemia patients with normal cytogenetics: a Cancer and Leukemia Group B Study.

Cytogenetic aberrations are important prognostic factors in acute myeloid leukemia (AML). Of adults with de novo AML, 45% lack cytogenetic abnormalities, and identification of predictive molecular markers might improve therapy. We studied the prognostic impact of BAALC (Brain And Acute Leukemia, Cytoplasmic), a novel gene involved in leukemia, in 86 de novo AML patients with normal cytogenetics who were uniformly treated on Cancer and Leukemia Group B 9621. BAALC expression was determined by comparative real-time reverse transcriptase-polymerase chain reaction in pretreatment blood samples, and patients were dichotomized at BAALC's median expression into low and high expressers. Low expressers had higher white counts (P =.03) and more frequent French-American-British M5 morphology (P =.007). Compared to low expressers, high BAALC expressers showed significantly inferior overall survival (OS; median, 1.7 vs 5.8 years, P =.02), event-free survival (EFS; median, 0.8 vs 4.9 years, P =.03), and disease-free survival (DFS; median, 1.4 vs 7.3 years, P =.03). Multivariable analysis confirmed high BAALC expression as an independent risk factor. For high BAALC expressers the hazard ratio of an event for OS, EFS, and DFS was respectively 2.7, 2.6, and 2.2. We conclude that high BAALC expression predicts an adverse prognosis and may define an important risk factor in AML with normal cytogenetics.

Acute Disease↗