Friederike H Kreisel

Washington University in St. Louis, San Luis, Missouri, United States

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Publications (49)155.21 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: In recent years, research has increasingly focused on the microenvironment of classical Hodgkin lymphoma (CHL) as a predictor of treatment outcome. The focus of this study was to assess the interobserver reproducibility in interpreting macrophage-associated immunohistochemistry (IHC) for CD68 and CD163 in a retrospective cohort of 88 patients with CHL. Methods: Staining results were correlated with clinical outcome in all patients and those with a high international prognostic score (IPS). Results: The intraclass correlation (ICC) for the five hematopathologists interpreting the IHC was stronger for CD163 (0.70) than for CD68 (0.50). Using a cutoff of 25% mean macrophage reactivity and including all patients, a statistically significant difference in overall survival (OS) was seen only for CD163 (P = .0006) and not for CD68 (P = .414). Patients with a mean CD163 reactivity of 25% or more had a median OS of 71 months vs 101 months for patients with less than 25% reactivity. CD163 retained statistical significance in multivariate analysis. In patients with advanced-stage CHL with high IPS, OS was also significantly worse for those with a mean CD163 reactivity of 25% or higher. Conclusions: Our study confirms previous reports of a prognostic role of tumor-infiltrating macrophages in CHL, but only for CD163. Although most of the literature supports an increasing role of macrophage IHC as a predictor of clinical outcome, successful clinical translation will require a standardized method and reporting system.
    American Journal of Clinical Pathology 03/2014; 141(3):381-7. · 2.88 Impact Factor
  • Andy C Hsi, Friederike H Kreisel, John L Frater, Tudung T Nguyen
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    ABSTRACT: Human T-cell lymphotropic virus type 1 is associated with adult T-cell leukemia/lymphoma (ATLL). Published series of ATLLs seen at a United States medical institution are rare. We present the features of 4 ATLLs diagnosed at our North American tertiary care medical center from 1990 to 2012. Despite the absence of a history of origin from an endemic region, all our ATLLs demonstrated evidence of human T-cell lymphotropic virus type 1 infection. Central nervous system (CNS) involvement by ATLL was uncommon in our series, and represented only 1.6% (1/64) of all CNS B-cell or T-cell lymphomas diagnosed over a 20+ year period at our institution. Review of the medical literature reveals that the majority of CNS-involved ATLLs present with the lymphoma or acute subtype, and complete remission is difficult to achieve in these cases. CNS involvement frequently occurs with a systemic disease, which carries an aggressive clinical course with poor prognosis. In addition, CNS involvement by ATLL can be the initial presentation or seen with relapsed disease, can be the only site or be associated with other tissue sites of involvement, and may manifest with variable clinical signs/symptoms. Our retrospective study reveals that ATLLs are rare mature T-cell lymphomas in a native North American population, but the clinical and histopathologic features of ATLLs from this nonendemic region are similar to those seen from other endemic regions. Early recognition of these rare ATLLs involving uncommon sites, such as the CNS, will help optimize treatment for these infrequent mature T-cell lymphomas.
    The American journal of surgical pathology 02/2014; 38(2):245-56. · 4.06 Impact Factor
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    ABSTRACT: Burkitt lymphoma (BL) is a rare, highly aggressive B-cell malignancy treated most successfully with brief-duration, high-intensity chemotherapeutic regimens. The benefit of the addition of rituximab to these regimens remains uncertain. We sought to examine the effectiveness of chemotherapy with and without rituximab in patients with BL. This study is a retrospective cohort study of all adult patients with BL diagnosed and treated with modern, dose-intense chemotherapeutic regimens from 1998-2008 at two tertiary care institutions. All cases were confirmed by application of WHO 2008 criteria by hematopathologists. Medical records were reviewed for patient-, disease-, and treatment- related factors as well as treatment response and survival. Factors associated with survival were analyzed using Cox proportional hazards modeling. A total of 35 patients were analyzed: 18 patients received rituximab with chemotherapy (R-chemo) and 17 received chemotherapy (chemo) alone. The median age was 42 (range 20-74 years); 57% were male; 71% had Ann Arbor Stage IV disease; 33% had central nervous system involvement; 78% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. R-chemo was associated with significantly longer overall survival (OS) than chemo alone (5-year OS 70% and 29%, respectively, p = 0.040). On multivariate regression analysis, poor performance status and central nervous system involvement were associated with poorer survival. The addition of rituximab to chemotherapy was associated with improved OS in patients with Burkitt lymphoma. Poor performance status and central nervous system involvement were prognostically significant on multivariate analysis.
    Therapeutic advances in hematology. 02/2014; 5(1):3-12.
  • Xiangdong Xu, Friederike H Kreisel, John L Frater, Anjum Hassan
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    ABSTRACT: Mast cell leukemia (MCL) is a rare and aggressive form of systemic mastocytosis. There are approximately 50 reported cases since 1950s. MCL is refractory to cytoreduction chemotherapy and the average survival is only six months. We report a MCL case in a 71 year-old woman with high tumor load at the initial presentation in 2005, who did not respond to either interleukin-2 or dasatinib therapy. After enrolled in a clinical trial of PKC412 (or Midostaurin) with a daily dose of 100 mg, the patient responded well to PKC412 and became transfusion independent in three months. Since then, her disease had been stably controlled. This is the first report of a high-tumor-load MCL case which achieved prolonged survival (101 months) by PKC 412. The 101-month overall survival is the longest among reported MCL cases in the English literature.
    International journal of clinical and experimental pathology. 01/2014; 7(6):3439-43.
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    ABSTRACT: Context.-Experiences at our institution show that flow cytometry analysis (FCA) has become routine clinical practice in the workup of patients with altered mental status, even if risk factors are low. Objective.-To assess diagnostic accuracy of combined FCA and cytology in the diagnosis of central nervous system lymphoma in an unselected patient population with neurologic symptoms, including patients with no history of lymphoma or suspicious radiology. Design.-Between 2001 and 2011, cerebrospinal fluid was submitted from 373 patients for lymphoma screening by FCA. The medical records were reviewed for patient symptomatology, history of malignancy, brain imaging, FCA results, cytology results, brain biopsy, and clinical follow-up. Results.-A lymphoid malignancy was detected by FCA in 4% of cases. A positive diagnosis was more likely in patients with either a history of hematologic malignancy and/or a suspicious radiology result (P = .009). All patients with no history of lymphoma and no suspicious radiology (n = 102) had negative cytology, and none had a correspondingly positive FCA result. The positive and negative predictive values of combined cytology and FCA in the patients with history of lymphoma and/or abnormal imaging results were 92% and 89%, respectively, when compared with open brain tissue biopsy, and 89% and 86%, respectively, when compared with clinical follow-up. When low-risk patients were included, the positive predictive value remained at 92%, but the negative predictive value dropped to 52% with the open brain biopsy as the reference, and values did not change significantly for the group with clinical follow-up. Conclusions.-Concurrent FCA and cytology are most useful in the appropriate clinical setting, and we propose a triage algorithm for how FCA on cerebrospinal fluid is best used.
    Archives of pathology & laboratory medicine 11/2013; 137(11):1610-8. · 2.78 Impact Factor
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    ABSTRACT: We present the case of a 30 year-old man who was referred for evaluation of diffuse lymphadenopathy. Six weeks prior, he noticed darkening of his urine as sociated with pale stools, nausea and an eventual 30 lb weight loss within a month. The initial laboratory findings showed elevation of the liver enzymes. A CT scan showed mesenteric and periaortic lymphadenopathy with the largest lymph node measuring 2.8 cm. Other laboratory results were otherwise unremarkable (including a normal LDH) with the exception of positive serum antibodies against Epstein-Barr virus (EBV) associated antigens (IgM+ and IgG+). An excisional biopsy of 4 of the small neck lymph nodes showed a normal architecture with prominent follicles and an intact capsule. But, by immunohistochemistry two of the follicles showed aberrant coexpression of BCL-2, in addition to CD10 and BCL-6. In-situ hybridization for early Epstein-Barr virus mRNA (EBER) and immunohistochemistry for latent membrane protein-1 (LMP-1) stained both scattered positive cells, as well as BCL-2 positive B-cells. Although an original diagnosis of in-situ follicular lymphoma was favored at an outside facility, additional interphase fluorescence in situ hybridization (FISH) studies for t(14;18);(IGH-BCL2) rearrangement (performed on the BCL-2 + follicles microdissected from the tissue block; Abott probe dual colour fusion) and molecular studies (IGH gene rearrangement by PCR, also performed on the microdissected follicles) were negative. Serologic studies (positive EBV antibodies) and immunostains in conjunction with the molecular studies confirmed the reactive nature of the changes. Our case also shows direct immunopathogenic evidence of BCL-2 expression among the EBV-infected cells, which has to our knowledge not been previously documented in vivo. A diagnosis of EBV infection should, therefore, be considered when confronted with BCL-2 expression in germinal centers, particularly in younger individuals, as the diagnosis of FLIS may lead to extensive and invasive haematologic work-ups. Virtual slides
    Diagnostic Pathology 06/2013; 8(1):100. · 1.85 Impact Factor
  • Journal of Clinical Oncology 06/2013; · 18.04 Impact Factor
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    ABSTRACT: This first study in humans was designed to evaluate the safety and dosimetry of a cellular proliferative marker, N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-(18)F-fluoroethoxy)-5-methylbenzamide ((18)F-ISO-1), and evaluate the feasibility of imaging tumor proliferation by PET in patients with newly diagnosed malignant neoplasms. METHODS: Patients with biopsy-proven lymphoma, breast cancer, or head and neck cancer underwent (18)F-ISO-1 PET. Tumor (18)F-ISO-1 uptake was assessed semiquantitatively by maximum standardized uptake value, ratios of tumor to normal tissue and tumor to muscle, and relative distribution volume ratio. The PET results were correlated with tumor Ki-67 and mitotic index, from in vitro assays of the tumor tissue. The biodistribution of (18)F-ISO-1 and human dosimetry were evaluated. RESULTS: Thirty patients with primary breast cancer (n = 13), head and neck cancer (n = 10), and lymphoma (n = 7) were evaluated. In the entire group, tumor maximum standardized uptake value and tumor-to-muscle ratio correlated significantly with Ki-67 (τ = 0.27, P = 0.04, and τ = 0.38, P = 0.003, respectively), but no significant correlation was observed between Ki-67 and tumor-to-normal-tissue ratio (τ = 0.07, P = 0.56) or distribution volume ratio (τ = 0.26, P = 0.14). On the basis of whole-body PET data, the gallbladder is the dose-limiting organ, with an average radiation dose of 0.091 mGy/MBq. The whole-body and effective doses were 0.012 mGy/MBq and 0.016 mSv/MBq, respectively. No adverse effects of (18)F-ISO-1 were encountered. CONCLUSION: The presence of a significant correlation between (18)F-ISO-1 and Ki-67 makes this agent promising for evaluation of the proliferative status of solid tumors. The relatively small absorbed doses to normal organs allow for the safe administration of up to 550 MBq, which is sufficient for PET imaging in clinical trials.
    Journal of Nuclear Medicine 01/2013; · 5.77 Impact Factor
  • International journal of laboratory hematology 12/2012; · 1.30 Impact Factor
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    ABSTRACT: We conducted a retrospective study of patients with cutaneous myeloid sarcoma, from 2 tertiary care institutions. Eighty-three patients presented, with a mean age of 52 years. Diagnosis of myeloid sarcoma in the skin was difficult due to the low frequency of myeloperoxidase and/or CD34+ cases (56% and 19% of tested cases, respectively). Seventy-one of the 83 patients (86%) had ≥ 1 bone marrow biopsy. Twenty-eight (39%) had acute myeloid leukemia with monocytic differentiation. Twenty-three had other de novo acute myeloid leukemia subtypes. Thirteen patients had other myeloid neoplasms, of which 4 ultimately progressed to an acute myeloid leukemia. Seven had no bone marrow malignancy. Ninety-eight percent of the patients received chemotherapy, and approximately 89% died of causes related to their disease. Cutaneous myeloid sarcoma in most cases represents an aggressive manifestation of acute myeloid leukemia. Diagnosis can be challenging due to lack of myeloblast-associated antigen expression in many cases, and difficulty in distinguishing monocyte-lineage blasts from neoplastic and non-neoplastic mature monocytes.
    Acta Dermato-Venereologica 11/2012;
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    ABSTRACT: INTRODUCTION: With proper logistical support and sponsorship, a laboratory in an industrialized nation might be able to act as a reference laboratory for clinicians based in a developing country. METHODS: We built on previous experience in the clinical laboratory to see whether a specialized histopathology service (hematopathology) could be provided to a developing country without the expertise or experience to do it in country. RESULTS: Over an 13-year period, 582 cases from 579 individuals were analyzed. Principal pathologic findings included acute leukemia in 84 cases (14%), dyspoiesis in one or more of the hematopoietic lineages in 65 cases (11%, including three cases with high-grade myelodysplasia), 23 cases (4%) with findings suspicious for a chronic myeloproliferative disorder, 35 cases (6%) with findings suspicious for a lymphoproliferative disorder, and infectious organisms (presumably Leishmania in most instances) in 9 (1%) of cases. Specimens from 45 cases (8%) were unsatisfactory owing to extreme hemodilution and/or specimen degeneration. CONCLUSION: With proper support, a medical laboratory in an industrialized nation may serve as a reference facility for a developing nation. The use of existing infrastructure may be remarkably effective to achieve optimal turnaround time. Although the lack of ancillary studies and follow-up biopsies limit the ability to achieve a definitive diagnosis in many cases, this must be viewed in the context of the limited ability to diagnose or manage hematopoietic neoplasia in developing nations.
    International journal of laboratory hematology 09/2012; · 1.30 Impact Factor
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    ABSTRACT: BACKGROUND: Gastrointestinal (GI) lymphomas are very common types of extranodal lymphomas, and we hypothesize there are regional differences in subtype, distribution in the GI tract, and epidemiological features among the different populations. METHODS: We retrospectively evaluated the clinical, molecular and histologic features of North American primary and secondary GI lymphomas diagnosed from 2000¿2009 seen at our institution. We utilized immunohistochemistry and fluorescence in situ hybridization to further evaluate a subset of the gastric lymphomas. RESULTS: Extranodal marginal zone lymphomas of mucosal associated lymphoid tissue (MALTs) and diffuse large B cell lymphomas (DLBCLs) were the most common subtypes of GI lymphomas. Select gastric DLBCLs (N¿=¿6) and MALTs (N¿=¿13) were further examined for API2-MALT1 and IGH translocations, and P16 and P53 protein expression. Gastric MALTs showed frequent API2-MALT1 (38%) but not IGH translocations (0%), and the DLBCLs showed neither translocation. Expression of P16 and P53 proteins and the proliferative index were compared between high grade gastric lymphomas (gastric DLBCLs) and low grade gastric lymphomas (gastric MALTs). P53 overexpression (P¿=¿0.008) and a high proliferation index [Ki-67] (P¿=¿0.00042) were significantly associated with gastric DLBCL, but no statistically significant difference was observed in P16 expression (p¿=¿0.108) between gastric DLBCL and gastric MALT. CONCLUSION: Our study revealed that GI lymphomas from a Central-Midwestern North American population showed differences and similarities to non-North American cohorts. In addition, API2-MALT1, P16 and P53 abnormalities occurred frequently in gastric lymphomas from this North American population. Virtual slides: The virtual slides for this article can be found here:
    Diagnostic Pathology 06/2012; 7(1):76. · 1.85 Impact Factor
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    ABSTRACT: Cutaneous myeloid sarcoma is often challenging to diagnose based solely upon histopathological features. Although immunohistochemistry can aid in its diagnosis, specific markers have not been clearly identified. We evaluated the utility of immunohistochemical markers in 57 cutaneous myeloid sarcoma cases. In addition to classical markers (CD117, CD163, CD34, myeloperoxidase and lysozyme), we used CD33 and CD14, recently described markers in paraffin-embedded tissue samples, and Kruppel-like factor 4 (KLF-4), a novel monocytic marker. Our results show that lysozyme was expressed in 91%, CD33 in 60%, myeloperoxidase in 54%, CD34 in 39% and CD117 in 36% of cases. An antibody panel that included lysozyme, CD117 and CD33 identified all cases. The monocytic markers CD14, KLF-4 and CD163 were expressed in 60, 58 and 40% of all cases, respectively. CD14 and KLF-4 expression was significantly more common in cases with monocytic differentiation. CD14 is the single most sensitive and specific marker for monocytic differentiation (79 and 80%). Although KLF-4 in isolation is relatively insensitive (50 and 87%), it enhances sensitivity in detecting monocytic cutaneous myeloid sarcoma when combined with CD14. Our results indicate that in addition to classical immunohistochemical markers, targeted use of newer antibodies, including CD33, CD14 and KLF-4 is useful in the diagnosis of cutaneous myeloid sarcoma and in the detection of monocytic differentiation.
    Journal of Cutaneous Pathology 12/2011; 38(12):945-53. · 1.77 Impact Factor
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    ABSTRACT: Myeloid sarcomas are extramedullary lesions composed of myeloid lineage blasts that typically form tumorous masses and may precede, follow, or occur in the absence of systemic acute myeloid leukemia. They most commonly involve the skin and soft tissues, lymph nodes, and gastrointestinal tract and are particularly challenging to diagnose in patients without an antecedent history of acute myeloid leukemia. We conducted a search of the English language medical literature for recent studies of interest to individuals involved in the diagnosis of myeloid sarcoma. The differential diagnosis includes non-Hodgkin lymphoma, blastic plasmacytoid dendritic cell neoplasm, histiocytic sarcoma, melanoma, carcinoma, and (in children) small round blue cell tumors. The sensitivity and specificity of immunohistochemical markers must be considered when evaluating a suspected case of myeloid sarcoma. A high percentage of tested cases have cytogenetic abnormalities. A minimal panel of immunohistochemical markers should include anti-CD43 or anti-lysozyme as a lack of immunoreactivity for either of these sensitive markers would be inconsistent with a diagnosis of myeloid sarcoma. Use of more specific markers of myeloid disease, such as CD33, myeloperoxidase, CD34 and CD117 is necessary to establish the diagnosis. Other antibodies may be added depending on the differential diagnosis. Identification of acute myeloid leukemia-associated genetic lesions may be helpful in arriving at the correct diagnosis.
    International journal of laboratory hematology 08/2011; 33(6):555-65. · 1.30 Impact Factor
  • Journal of clinical pathology 07/2011; 64(11):1032-4. · 2.43 Impact Factor
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    Friederike Kreisel
    Cytometry Part B Clinical Cytometry 07/2011; 80(4):255-7. · 2.23 Impact Factor
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    ABSTRACT: Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are regarded as the same entity, with SLL restricted to tissue cases featuring no leukemic phase. In this study, the authors evaluate a group of SLL cases for cytogenetic abnormalities and IgVH gene mutational status to illicit differences between CLL and SLL. IgVH gene polymerase chain reaction amplification and subsequent sequencing were preformed on formalin-fixed, paraffin-embedded archival tissue of 44 patients (SLL n = 34 or CLL n = 10). Cytogenetic data, CD38, and ZAP-70 expression were also evaluated for these cases. The data indicate that 9/34 (26%) SLL cases have somatic hypermutation >2%, which is less than the CLL group where 40% were mutated (4/10). Cytogenetic abnormalities were seen in 58% of the SLL cases with many showing abnormalities associated with favorable to intermediate prognosis. The authors' attempt to compare CLL with SLL with regards to cytogenetic and IgVH mutational status shows no statistically significant difference.
    International Journal of Surgical Pathology 05/2011; 19(5):563-9. · 0.76 Impact Factor
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    ABSTRACT: Detection of monocytic differentiation in myeloid neoplasms by immunohistochemical analysis is challenging owing to a lack of sensitive and/or specific antibodies. We tested the usefulness of immunohistochemical analysis for CD14, an antigen commonly detected by flow cytometry, and Krüppel-like factor 4 (KLF4), a potentially novel marker of monocytic differentiation, in a series of myeloid leukemias, including 53 acute myeloid leukemias with monocytic differentiation. These findings were compared with immunohistochemical findings for CD68 (KP-1), CD34, and CD163 and were also correlated with flow cytometric and enzyme cytochemical results. CD163 and CD14 are the most specific markers of monocytic differentiation, followed by KLF4. CD68, in contrast, is the most sensitive monocytic marker, and KLF4 is also significantly more sensitive than CD14 and CD163. These studies show that KLF4 is another marker of monocytic differentiation and that the combination of CD14 and CD163 can increase the diagnostic sensitivity for monocytic neoplasms.
    American Journal of Clinical Pathology 05/2011; 135(5):720-30. · 2.88 Impact Factor
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    ABSTRACT: Core needle biopsy (CNB) and fine-needle aspiration (FNA) are increasingly replacing excisional lymph node biopsy in the diagnosis of lymphomas. However, evaluation of CNB and FNA remains challenging owing to limited architectural information and the more detailed subclassification of lymphomas required by the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Our study is the largest study to assess diagnostic accuracy of CNB and FNA in conjunction with ancillary studies. We analyzed 263 cases and a diagnosis was established in 237, of which 193 were completely subclassified. In cases in which excisional biopsy was available as a reference for comparison, CNB and FNA had a sensitivity of 96.5%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 90%. CNB and FNA with ancillary studies represent a viable alternative in the diagnosis of lymphoma, as long as the number and size of cores for morphologic studies are not compromised.
    American Journal of Clinical Pathology 04/2011; 135(4):516-24. · 2.88 Impact Factor
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    ABSTRACT: Despite recent attempts at sub-categorization, including gene expression profiling into prognostically different groups of "germinal center B-cell type" and "activated B-cell type," diffuse large B-cell lymphoma (DLBCL) remains a biologically heterogenous tumor with no clear prognostic biomarkers to guide therapy. Whole genome, high resolution array comparative genomic hybridization (aCGH) was performed on four cases of chemoresistant DLBCL and four cases of chemo-responsive DLBCL to identify genetic differences that may correlate with response to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Array CGH analysis identified seven DNA copy number alteration (CNA) regions exclusive to the chemoresistant group, consisting of amplifications at 1p36.13, 1q42.3, 3p21.31, 7q11.23, and 16p13.3, as well as loss at 9p21.3 and 14p21.31. Copy number loss of the tumor suppressor genes CDKN2A (p16, p14) and CDKN2B (p15) at 9p21.3 was validated by fluorescence in situ hybridization and immunohistochemistry as independent techniques. In the chemo-sensitive group, 12 CNAs were detected consisting of segment gains on 1p36.11, 1p36.22, 2q11.2, 8q24.3, 12p13.33, and 22q13.2, as well as segment loss on 6p21.32. RUNX3, a tumor suppressor gene located on 1p36.11 and MTHFR, which encodes for the enzyme methylenetetrahydrofolate reductase, located on 1p36.22, are the only known genes in this group associated with lymphoma. Whole genome aCGH analysis has detected copy number alterations exclusive to either chemoresistant or chemoresponsive DLBCL that may represent consistent clonal changes predictive for prognosis and outcome of chemotherapy.
    Cancer Genetics 03/2011; 204(3):129-37. · 1.92 Impact Factor

Publication Stats

364 Citations
155.21 Total Impact Points


  • 2006–2014
    • Washington University in St. Louis
      • • Department of Pathology and Immunology
      • • Department of Surgery
      San Luis, Missouri, United States
  • 2012
    • Saint Louis University
      • Department of Dermatology
      Saint Louis, Michigan, United States
  • 2005–2011
    • University of Washington Seattle
      • • Department of Immunology
      • • Department of Surgery
      Seattle, WA, United States