Mark Pettenati | Wake Forest University School of Medicine (original) (raw)

Papers by Mark Pettenati

Journal of clinical pathology, 2015

Near-tetraploidy/tetraploidy (NT/T) is a rare cytogenetic alteration in acute myeloid leukaemia (... more Near-tetraploidy/tetraploidy (NT/T) is a rare cytogenetic alteration in acute myeloid leukaemia (AML). NT/T-AML is categorised as complex cytogenetics and therefore, presumed to have an unfavourable prognosis. Our aim is to further characterise the clinical, morphological, cytogenetic and prognostic features of NT/T-AML. We searched our cytogenetic laboratory database from 1991 to 2012 to reveal 13 cases of NT/T-AML. Each case was evaluated with regard to its demographics, morphology, immunophenotype and prognosis. Specific morphological features included blast size, irregularity of nuclear contours, cytoplasmic vacuoles, and presence and lineage of dysplasia. Eleven men and two women had a median age of 68 years. Blasts were predominately large (11/13). Eight of 13 patients had AML with myelodysplasia-related changes. Sixty-nine per cent of patients achieved complete remission (CR). Median overall survival (OS) was 8.6 months. CR rate and median OS in cases with ≥5 cytogenetic abno...

IEEE Transactions on Plasma Science, 2006

Background: Interest in the use of extremely low-frequency (ELF) electromagnetic field (EMF) for ... more Background: Interest in the use of extremely low-frequency (ELF) electromagnetic field (EMF) for the treatment of pain and inflammation is increasing due to the ability of this promising therapy to compete with pharmaceuticals without the adverse effects caused by drugs. However, there continues to be concerns regarding cytotoxic and genotoxic effects that may occur as a result of exposure to EMF. Objective: To investigate this concern, we tested the effect of our known therapeutic 5 Hz, 0.4 milliTesla (mT) EMF on a human mesenchymal stromal cell (hMSC) line to determine whether ELF-EMF exposure would cause cytotoxic or genotoxic effects. Methods: Treated samples along with controls were exposed to 5 Hz, 0.4 mT ELF-EMF for 20 min/day, 3Â/week for 2 weeks and then assayed for cell viability, proliferation rates, and chromosome breaks. Results: Cytogenetic analysis of the viability and proliferation rates along with analysis of morphological genome stability showed no cytotoxicity, and no chromosome breaks per karyotype analysis-therefore no genotoxicity. Conclusion: Exposure to an ELF-EMF of 5 Hz, 0.4 mT for 20 min/day, 3Â/week for 2 weeks does not cause cytotoxic or genotoxic effects in hMSCs.

Blood, 2007

Pediatric Oncology Group (POG) protocol 9201 enrolled children with lesser-risk B-lineage acute l... more Pediatric Oncology Group (POG) protocol 9201 enrolled children with lesser-risk B-lineage acute lymphoblastic leukemia (ALL) defined by age (1-9), white blood cell count (WBC) less than 50 × 109/L (50 000/μL), DNA findings of trisomies 4 and 10 (or DNA index > 1.16), and lack of overt central nervous system (CNS) leukemia. After vincristine, prednisone, and asparaginase induction, 650 of 653 eligible patients attained remission (3 induction deaths) and received 6 courses of intravenous methotrexate (1 g/m2) with daily mercaptopurine. Weekly intramuscular methotrexate was added during maintenance; pulses of vincristine and prednisone were administered with periodic intrathecal chemotherapy. Treatment duration was 2.5 years. No alkylators, epipodophylotoxins, anthracyclines, or radiation were given. The 6-year event-free survival (EFS) was 86.6% with overall survival (OS) of 97.2%. Patients with less than 5% marrow blasts on induction day 15 had superior EFS. A difference not reach...

Annals of Hematology, 2006

Recent reports suggest that hemopoietic stem cells with constitutional pericentric inversion of c... more Recent reports suggest that hemopoietic stem cells with constitutional pericentric inversion of chromosome 9 [inv(9)] may be related to delayed engraftment or hemopoietic defect after stem cell transplantation (SCT). We conducted a retrospective study on five allogeneic SCT in which constitutional inv(9) was detected either in the donor or the recipient. The results showed that hematologic recovery was within the expected time range for all our patients. However, one patient exhibited decreasing blood counts between day +45 and +272 after transplantation, possibly due to protracted cytomegalovirus (CMV) infection and gansiclovir and imatinib treatment. Our findings suggest that constitutional inv(9) may not be associated with delayed hemopoietic recovery after SCT.

Pediatric Blood & Cancer, 2007

The diagnosis of Burkitt lymphoma by thoracentesis has been rarely reported in the literature, pa... more The diagnosis of Burkitt lymphoma by thoracentesis has been rarely reported in the literature, particularly in children. From 1995 to 2004, we diagnosed six pediatric patients with mature B-cell neoplasms using thoracentesis as the initial diagnostic procedure. The cytology, immunophenotyping, and cytogenetic results of the pleural fluid cells were consistent with mature B-cell malignancies. We conclude that thoracentesis for the diagnosis of Burkitt lymphoma in children is safe, fast, and accurate. It should be strongly considered as an initial diagnostic procedure for pediatric patients with pleural effusions who are suspected of having B-cell malignancies.

Journal of Clinical Oncology, 2005

Purpose Because both t(8;21) and inv(16) disrupt core binding factor (CBF) in acute myeloid leuke... more Purpose Because both t(8;21) and inv(16) disrupt core binding factor (CBF) in acute myeloid leukemia (AML) and confer relatively favorable prognoses, these cytogenetic groups are often treated similarly. Recent studies, however, have shown different gene profiling for the two groups, underscoring potential biologic differences. Therefore, we sought to determine whether these two cytogenetic groups should also be considered separate entities from a clinical standpoint. Patients and Methods We analyzed 144 consecutive adults with t(8;21) and 168 with inv(16) treated on Cancer and Leukemia Group B front-line studies. We compared pretreatment features, probability of achieving complete remission (CR), overall survival (OS) and cumulative incidence of relapse (CIR) between the two groups. Results With a median follow-up of 6.4 years, for CBF AML as a whole, the CR rate was 88%, 5-year OS was 50% and CIR was 53%. After adjusting for covariates, patients with t(8;21) had shorter OS (hazard...

Journal of Clinical Oncology, 2012

Purpose To evaluate the prognostic significance of the international European LeukemiaNet (ELN) g... more Purpose To evaluate the prognostic significance of the international European LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid leukemia (AML). Patients and Methods We analyzed 1,550 adults with primary AML, treated on Cancer and Leukemia Group B first-line trials, who had pretreatment cytogenetics and, for cytogenetically normal patients, mutational status of NPM1, CEBPA, and FLT3 available. We compared complete remission (CR) rates, disease-free survival (DFS), and overall survival (OS) among patients classified into the four ELN genetic groups (favorable, intermediate-I, intermediate-II, adverse) separately for 818 younger (age < 60 years) and 732 older (age ≥ 60 years) patients. Results The percentages of younger versus older patients in the favorable (41% v 20%; P < .001), intermediate-II (19% v 30%; P < .001), and adverse (22% v 31%; P < .001) genetic groups differed. The favorable group had the best and the adverse group the worst CR ...

Human Heredity, 2000

Chromosome 9q34 has been extensively studied and mapped due to the presence of known disease gene... more Chromosome 9q34 has been extensively studied and mapped due to the presence of known disease genes, principally tuberous sclerosis 1 (TSC1), in this region. During the course of our mapping of this region we constructed a 555-kb contig beginning approximately 50 kb proximal to the dopamine-β-hydroxylase (DBH) gene and extending, with one small deletion, distal to the D9S114 marker. The contig consists of 11 P1 clones, four PAC clones, one BAC clone and six cosmid clones and contains 27 new nonpolymorphic STSs. We have found the region to be unstable in P1, PAC and BAC cloning vehicles and have identified several deleted genomic clones. In addition, we have isolated and mapped the 3′ portions of three putative genes located within or immediately distal to the DBH gene, including one large gene that runs on the opposite strand to DBH and utilizes portions of two DBH exons. The genomic clones of the contig, cDNAs and new STSs will be useful reagents for the further study and mapping of...

Genomics, 1995

The genomic structure of the DZOS16 locus has been evaluated using genetic and physical methods. ... more The genomic structure of the DZOS16 locus has been evaluated using genetic and physical methods. D20S16, originally detected with the probe CRI-L1214, is a highly informative, complex restriction fragment length polymorphism consisting of two separate allelic systems. The allelic systems have the characteristics of conventional VNTR polymorphisms and are separated by recombination (6 = 0.02, Z,,, = 74.821, as demonstrated in family studies. Most of these recombination events are meiotic crossovers and are maternal in origin, but two, including deletion of the locus in a cell line from a CEPH family member, occur without evidence for exchange of flanking markers. DNA sequence analysis suggests that the basis of the polymorphism is variable numbers of a 98-bp sequence tandemly repeated with 8'7 to 90% sequence similarity between repeats. The 98-bp repeat is a dimer of 49 bp sequence with 45 to 98% identity between the elements. In addition, nonpolymorphic genomic sequences adjacent to the polymorphic 98-bp repeat tracts are also repeated but are not polymorphic, i.e., show no individual to individual variation. Restriction enzyme mapping of cosmids containing the CRI-L1214 sequence suggests that there are multiple interspersed repeats of the CRI-L1214 sequence on chromosome 20. The results of dual-color fluorescence in situ hybridization experiments with interphase nuclei are also consistent with multiple repeats of an interspersed sequence on chromosome 20.

Genetics in Medicine, 1999

To evaluate the assumptions on which the American College of Medical Genetics (ACMG) Standards an... more To evaluate the assumptions on which the American College of Medical Genetics (ACMG) Standards and Guidelines for detecting mosaicism in amniotic fluid cultures are based. Methods: Data from 653 cases of amniotic fluid mosaicism were collected from 26 laboratories. A chi-square goodness-of-fit test was used to compare the observed number of mosaic cases with the expected number based on binomial distribution theory. Results: Comparison of observed data from the in situ colony cases with the expected distribution of cases detected based on the binomial distribution did not reveal a significant difference (P = 0.525). Conclusions: The empirical data fit the binomial distribution. Therefore, binomial theory can be used a s an initial discussion point for determining whether ACMG Standards and Guidelines are adequate for detecting mosaicism. Genetics in Medicine, 1999;1(3):94-97

Clinical Genetics, 2008

We report a 2-year-old female with seizures, mild dysmorphic features and a jumping translocation... more We report a 2-year-old female with seizures, mild dysmorphic features and a jumping translocation involving chromosome 15 that results in multiple cell lines with partial duplications and triplications of chromosomes 7 and 15. Fluorescent in situ hybridization (FISH) and chromosome microdissection were used to identify the complex nature of the jumping translocation. Interstitial telomeres were observed at the jumping translocation sites. The jumping chromosome rearrangement was also found to have a partial duplication of 7p as demonstrated by chromosome microdissection. Despite these partial duplications and triplications of chromosomes 7 and 15, the child does not have major birth defects. She does have mild sensorimotor delays. A review of non-Robertsonian jumping translocations is provided.

Blood, 2012

The inv(16)(p13q22)/t(16;16)(p13;q22) in acute myeloid leukemia results in multiple CBFB-MYH11 fu... more The inv(16)(p13q22)/t(16;16)(p13;q22) in acute myeloid leukemia results in multiple CBFB-MYH11 fusion transcripts, with type A being most frequent. The biologic and prognostic implications of different fusions are unclear. We analyzed CBFB-MYH11 fusion types in 208 inv(16)/t(16;16) patients with de novo disease, and compared clinical and cytogenetic features and the KIT mutation status between type A (n = 182; 87%) and non–type A (n = 26; 13%) patients. At diagnosis, non–type A patients had lower white blood counts (P = .007), and more often trisomies of chromosomes 8 (P = .01) and 21 (P < .001) and less often trisomy 22 (P = .02). No patient with non–type A fusion carried a KIT mutation, whereas 27% of type A patients did (P = .002). Among the latter, KIT mutations conferred adverse prognosis; clinical outcomes of non–type A and type A patients with wild-type KIT were similar. We also derived a fusion-type–associated global gene-expression profile. Gene Ontology analysis of the ...

Skeletal Radiology, 1999

Sarcomas infrequently develop in osseous sites of fibrous dysplasia. We report a patient with Maz... more Sarcomas infrequently develop in osseous sites of fibrous dysplasia. We report a patient with Mazabraud's syndrome (polyostotic fibrous dysplasia and soft tissue myxomas) complicated by the development of osteogenic sarcoma in a bone affected by fibrous dysplasia. This is the third case of osteosarcoma within the small population of reported patients with Mazabraud's syndrome. There may be an increased incidence of malignant transformation in these individuals' dysplastic bones above that associated with patients suffering from fibrous dysplasia alone.

Proceedings of the National Academy of Sciences, 1987

The CSF-1 gene encodes a hematopoietic colony-stimulating factor (CSF) that promotes growth, diff... more The CSF-1 gene encodes a hematopoietic colony-stimulating factor (CSF) that promotes growth, differentiation, and survival of mononuclear phagocytes. By using somatic cell hybrids and in situ hybridization, we localized this gene to human chromosome 5 at bands q31 to q35, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the CSF-1 gene was found to be deleted in the 5q- chromosome of a patient with refractory anemia who had a del(5)(q15q33.3) and in that of a second patient with acute nonlymphocytic leukemia de novo who had a similar distal breakpoint [del(5)(q13q33.3)]. The gene was present in the deleted chromosome of a third patient, with therapy-related acute nonlymphocytic leukemia, who had a more proximal breakpoint in band q33 [del(5)(q22q33.1)]. Hybridization of the CSF-1 probe to metaphase cells of a fourth patient, with acute nonlymphocytic leukemia de novo, who had a rearrangement of chromosomes 5 and 2...

The Bethlem myopathy, a childhood onset autosomal dominant myopathy with joint contractures, has ... more The Bethlem myopathy, a childhood onset autosomal dominant myopathy with joint contractures, has recently been localized to 21q in a series of Dutch families and the α1 and α2 subunits of type VI collagen (COL6A1 and COL6A2) have been postulated as candidate genes. We investigate a large family of French Canadian descent (family 1489) in which the Bethlem myopathy is segregating. Family 1489 is unlinked to the region of interest on 21q, thus demonstrating locus heterogeneity within the Bethlem myopathy classification. In view of the localization of the genes coding the α1 and α2 subunits of type VI collagen on chromosome 21q, we carried out linkage analysis on chromosome 2q where the α3 subunit of type VI collagen has been localized. We demonstrate linkage to markers in this region, define the region of disease gene localization, and confirm by FISH analysis that COL6A3 is located within the interval of interest making COL6A3 a feasible candidate gene for the Bethlem myopathy.

International Journal of Molecular Sciences

Klinefelter syndrome (KS) is characterized by a masculine phenotype, supernumerary sex chromosome... more Klinefelter syndrome (KS) is characterized by a masculine phenotype, supernumerary sex chromosomes (usually XXY), and spermatogonial stem cell (SSC) loss in their early life. Affecting 1 out of every 650 males born, KS is the most common genetic cause of male infertility, and new fertility preservation strategies are critically important for these patients. In this study, testes from 41, XXY prepubertal (3-day-old) mice were frozen-thawed. Isolated testicular cells were cultured and characterized by qPCR, digital PCR, and flow cytometry analyses. We demonstrated that SSCs survived and were able to be propagated with testicular somatic cells in culture for up to 120 days. DNA fluorescent in situ hybridization (FISH) showed the presence of XXY spermatogonia at the beginning of the culture and a variety of propagated XY, XX, and XXY spermatogonia at the end of the culture. These data provide the first evidence that an extra sex chromosome was lost during innate SSC culture, a crucial f...

To the Editor: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematol... more To the Editor: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematologic neoplasm derived from plasmacytoid dendritic cells, which play a role between the innate and adaptive immune system.1 Themajority of reported cases of BPDCN have been in adults; however, 74 pediatric cases have reported as of 2017.2 Previous studies have shown a recurring subset of BPDCN that involve the MYC gene on 8q24 involving 10% to 41% of cases.3–5 Mutations involving the MYC gene have been associated with a worse prognosis and older patients. The most commonly reported mutation involving MYC with is t(6;8)(p21;q24). Only two pediatric cases involving MYC mutations have been previously reported. These involved t(2;8)(p12;q24) and t(X;8)(q24;q24.1), neither of which has been reported in adults.5 Interestingly, both pediatric cases withMYC mutations also harbored an ETV6 mutation. We present a case of the third known pediatric MYC mutation in BPDCN and the second case involving ...