Nicholas Chiorazzi

The Feinstein Institute for Medical Research, New York City, New York, United States

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Publications (203)1425.19 Total impact

  • Shih-Shih Chen, Nicholas Chiorazzi
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    ABSTRACT: Chronic lymphocytic leukemia (CLL) is a genetically complex disease, with multiple factors impacting on onset, progression, and response to therapy. Genetic differences/abnormalities have been found in hematopoietic stem cells from patients, as well as in B lymphocytes of individuals with monoclonal B-lymphocytosis that may develop the disease. Furthermore, after the onset of CLL, additional genetic alterations occur over time, often causing disease worsening and altering patient outcomes. Therefore, being able to genetically-engineer mouse models that mimic CLL or at least certain aspects of the disease help understand disease mechanisms and improve treatments. This notwithstanding, since neither the genetic aberrations responsible for leukemogenesis and progression nor the promoting factors that support these are likely identical in character or influences for all patients, genetically-engineered mouse models will only completely mimic CLL when all of these factors are precisely defined. In addition, multiple genetically-engineered models may be required because of the heterogeneity in susceptibility genes among patients that impact on genetic and environmental characteristics influencing disease development and outcome. For these reasons, in this chapter we review the major murine genetically-engineered and human xenograft models in use at the present time, aiming to report the advantages and disadvantages of each.
    Seminars in Hematology 01/2014; · 3.36 Impact Factor
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    ABSTRACT: B-cell chronic lymphocytic leukemia (B-CLL) patients expressing unmutated immunoglobulin heavy variable regions (IGHVs) use the IGHV1-69 B cell receptor (BCR) in 25% of cases. Since HIV-1 envelope gp41 antibodies also frequently use IGHV1-69 gene segments, we hypothesized that IGHV1-69 B-CLL precursors may contribute to the gp41 B cell response during HIV-1 infection. To test this hypothesis, we rescued 5 IGHV1-69 unmutated antibodies as heterohybridoma IgM paraproteins and as recombinant IgG1 antibodies from B-CLL patients, determined their antigenic specificities and analyzed BCR sequences. IGHV1-69 B-CLL antibodies were enriched for reactivity with HIV-1 envelope gp41, influenza, hepatitis C virus E2 protein and intestinal commensal bacteria. These IGHV1-69 B-CLL antibodies preferentially used IGHD3 and IGHJ6 gene segments and had long heavy chain complementary determining region 3s (HCDR3s) (≥21 aa). IGHV1-69 B-CLL BCRs exhibited a phenylalanine at position 54 (F54) of the HCDR2 as do rare HIV-1 gp41 and influenza hemagglutinin stem neutralizing antibodies, while IGHV1-69 gp41 antibodies induced by HIV-1 infection predominantly used leucine (L54) allelic variants. These results demonstrate that the B-CLL cell population is an expansion of members of the innate polyreactive B cell repertoire with reactivity to a number of infectious agent antigens including intestinal commensal bacteria. The B-CLL IGHV1-69 B cell usage of F54 allelic variants strongly suggests that IGHV1-69 B-CLL gp41 antibodies derive from a restricted B cell pool that also produces rare HIV-1 gp41 and influenza hemagglutinin stem antibodies.
    PLoS ONE 01/2014; 9(3):e90725. · 3.73 Impact Factor
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    ABSTRACT: Within T-cell-dependent germinal centers, p53 gene transcription is repressed by Bcl-6 and is thus less vulnerable to mutation. Malignant lymphomas within inflamed extranodal sites exhibit a relatively high incidence of p53 mutations. The latter might originate from normal B-cell clones manifesting activation-induced cytosine deaminase (AID) and up-regulated p53 following T-cell-independent (TI) stimulation. We here examine p53 gene transcription in such TI clones, with a focus on modulatory effects of prostaglandin E2 (PGE2), and evaluate progeny for p53 mutations. Resting IgM(+)IgD(+)CD27(-) B cells from human tonsils were labeled with CFSE and stimulated in vitro with complement-coated antigen surrogate, IL-4, and BAFF ± exogenous PGE2 (50 nM) or an analog specific for the EP2 PGE2 receptor. We use flow cytometry to measure p53 and AID protein within variably divided blasts, qRT-PCR of p53 mRNA from cultures with or without actinomycin D to monitor mRNA transcription/stability, and single-cell p53 RT-PCR/sequencing to assess progeny for p53 mutations. We report that EP2 signaling triggers increased p53 gene transcriptional activity in AID(+) cycling blasts (P<0.01). Progeny exhibit p53 mutations at a frequency (8.5×10(-4)) greater than the baseline error rate (<0.8×10(-4)). We conclude that, devoid of the repressive influences of Bcl-6, dividing B lymphoblasts in inflamed tissues should display heightened p53 transcription and increased risk of p53 mutagenesis.-Haque, S., Yan, X. J., Rosen, L., McCormick, S., Chiorazzi, N., Mongini, P. K. A. Effects of prostaglandin E2 on p53 mRNA transcription and p53 mutagenesis during T-cell-independent human B-cell clonal expansion.
    The FASEB Journal 10/2013; · 5.70 Impact Factor
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    ABSTRACT: For antigen recognition, lampreys use leucine-rich repeats (LRR) instead of immunoglobulin V-(D)-J domains to generate variable lymphocyte receptors (VLR) of three types, VLRA, VLRB, and VLRC. VLRB-bearing lymphocytes respond to immunization with proliferation and differentiation into plasmacytes that secrete multivalent VLRB antibodies. Here we immunized lampreys with B cells from patients with chronic lymphocytic leukemia (CLL) to generate recombinant monoclonal VLRB antibodies, one of which, VLR39, was specific for the donor CLL cells. The target epitope of VLR39 was shown to be the complementarity determining region 3 (CDR3) of the heavy chain variable region (VH) of the B cell receptor. Using this antibody to monitor the CLL donor after chemo-immunotherapy-induced remission, we detected VLR39(+) B cells in the patient 51 months later, before significant increase in lymphocyte count or CD5(+) B cells. This indication of reemergence of the leukemic clone was verified by VH sequencing. Lamprey antibodies can exhibit exquisite specificity for a protein epitope, a CLL signature VH CDR3 sequence in this case, and offer a rapid strategy for generating anti-idiotype antibodies for early detection of leukemia recurrence.
    Cancer immunology research. 10/2013; 1(4):223-228.
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    ABSTRACT: ABSTRACT Array comparative genomic hybridization (aCGH) has yet to be fully leveraged in a prognostic setting in chronic lymphocytic leukemia (CLL). Genomic imbalance was assessed in 288 CLL specimens using a targeted array. Based on 20 aberrations in a hierarchical manner, all 228 treatment-naive specimens were classified into a group with poor outcome (20.6%) exhibiting at least one aberration that univariately associated with adverse outcome (gain: 2p, 3q, 8q, 17q, loss: 7q, 8p, 11q, 17p, 18p), good outcome (32.5%) showing 13q14 loss without any of the other ten aberrations (gain: 1p, 7p, 12, 18p, 18q, 19, loss: 4p, 5p, 6q, 7p), or intermediate outcome (remainder). The three groups significantly separated with respect to time to first treatment and overall survival (P<0.001) and validation of the stratification scheme was performed in two independent datasets. Gain of 3q and 8q, and 17p loss were determined to be independent unfavorable prognostic biomarkers. TP53, NOTCH1, and SF3B1 mutations correlated with the presence of one poor outcome aCGH marker, at a considerably higher frequency than when only considering poor risk aberrations routinely detected by FISH. These data support genomic imbalance evaluation in CLL by aCGH to assist in risk stratification.
    Leukemia & lymphoma 09/2013; · 2.61 Impact Factor
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    ABSTRACT: Chronic lymphocytic leukemia (CLL) is a clonal disease of a subset of human B lymphocytes. Although the cause of the disease is unknown, its development and evolution appear to be promoted by signals delivered when B-cell receptors (BCRs) engage (auto)antigens. Here, using a peptide phage display library of enhanced size and diverse composition, we examined the binding specificity of a recombinant monoclonal antibody (mAb) constructed with the heavy chain and light chain variable domains of a CLL BCR that does not exhibit somatic mutations. As determined by testing the peptides identified in the selected peptide phage pool, this CLL-associated unmutated mAb bound a diverse set of sequences, some of which clustered in families based on amino acid sequence. Synthesis of these peptides and characterization of binding with the CLL-associated mAb revealed that mAb-peptide interactions were generally specific. Moreover, the mAb-peptide interactions were of lower affinities (micromolar KD), as measured by surface plasmon resonance, than those observed with a CLL mAb containing somatic mutations (nanomolar KD) and with IGHV-mutated antibodies selected by environmental antigens. This information may be of value in identifying and targeting B lymphocytes expressing specific BCRs in CLL patients and healthy subjects with monoclonal B lymphocytosis.
    Molecular Medicine 08/2013; · 4.47 Impact Factor
  • Piers E. M. Patten, Charles C. Chu, Nicholas Chiorazzi
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    ABSTRACT: Chronic lymphocytic leukemia (CLL) comprises 90% of chronic lymphoid leukemias in the USA and Europe, and contributes 6.7% of total cases of non-Hodgkin lymphoma [1]. It is a neoplasm of relatively monomorphic, small, round B lymphocytes with a characteristic immunophenotype. These cells reside in the peripheral blood, bone marrow and lymph nodes. Small lymphocytic lymphoma has a very similar immunophenotype to that of CLL, presenting with lymphadenopathy as opposed to lymphocytosis. CLL has an extremely variable natural history with survival from diagnosis ranging from months to decades. Some individuals require little or therapeutic intervention and enjoy a normal life expectancy, whereas others require multiple courses of treatment and ultimately die from the disease. The disease is incurable.
    06/2013: pages 196-214; , ISBN: eBook ISBN: 978-1-78084-171-7
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    ABSTRACT: Ag selection has been suggested to play a role in chronic lymphocytic leukemia (CLL) pathogenesis, but no large-scale analysis has been performed so far on the structure of the Ag-binding sites (ABSs) of leukemic cell Igs. We sequenced both H and L chain V(D)J rearrangements from 366 CLL patients and modeled their three-dimensional structures. The resulting ABS structures were clustered into a small number of discrete sets, each containing ABSs with similar shapes and physicochemical properties. This structural classification correlates well with other known prognostic factors such as Ig mutation status and recurrent (stereotyped) receptors, but it shows a better prognostic value, at least in the case of one structural cluster for which clinical data were available. These findings suggest, for the first time, to our knowledge, on the basis of a structural analysis of the Ab-binding sites, that selection by a finite quota of antigenic structures operates on most CLL cases, whether mutated or unmutated.
    The Journal of Immunology 05/2013; · 5.52 Impact Factor
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    ABSTRACT: Recent studies have revealed recurrent mutations of the NOTCH1, SF3B1 and BIRC3 genes in chronic lymphocytic leukemia (CLL), especially among aggressive, chemorefractory cases. Nevertheless, it is currently unknown whether their presence may differ in subsets of patients carrying stereotyped B-cell receptors (BcR) and also exhibiting distinct prognoses. Here, we analyzed the mutation status of NOTCH1, SF3B1 and BIRC3 in three subsets with particularly poor prognosis, i.e. subsets #1, #2 and #8, aiming to explore links between genetic aberrations and immune signaling. A remarkably higher frequency of SF3B1 mutations was revealed in subset #2 (44%) versus subsets #1 and #8 (4.6% and 0%, respectively; P<0.001). In contrast, the frequency of NOTCH1 mutations in subset #2 was only 8%; lower than the frequency observed in either subset #1 or #8 (19% and 14%, respectively; P=0.04 for subset #1 versus #2). No associations were found for BIRC3 mutations that overall were rare. The apparent non-random association of certain mutations with stereotyped CLL subsets alludes to subset-biased acquisition of genomic aberrations, perhaps consistent with particular antigen/antibody interactions. These novel findings assist in unraveling specific mechanisms underlying clinical aggressiveness in poor-prognostic stereotyped subsets, with far-reaching implications for understanding their clonal evolution and implementing biologically-oriented therapy.Leukemia accepted article preview online, 5 April 2013; doi:10.1038/leu.2013.98.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 04/2013; · 10.16 Impact Factor
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    ABSTRACT: (Auto)antigen engagement by the B-cell receptor (BCR) and possibly the sites where this occurs influence the outcome of chronic lymphocytic leukemia (CLL). To test if selection for autoreactivity leads to increased aggressiveness and if this selection plays out equally in primary and secondary tissues, we used T-cell leukemia (TCL)1 cells reactive with the autoantigen phosphatidylcholine (PtC). After repeated transfers of splenic lymphocytes from a single mouse with oligoclonal PtC-reactive cells, outgrowth of cells expressing a single IGHV-D-J rearrangement and superior PtC-binding and disease virulence occurred. In secondary tissues, increased PtC-binding correlated with enhanced BCR signaling and cell proliferation, whereas reduced signaling and division of cells from the same clone was documented in cells residing in the bone marrow, blood, and peritoneum, even though cells from the last site had highest surface membrane IgM density. Gene-expression analyses revealed reciprocal changes of genes involved in BCR-, CD40-, and PI3K-signaling between splenic and peritoneal cells. Our results suggest autoantigen-stimulated BCR signaling in secondary tissues promotes selection, expansion, and disease progression by activating pro-oncogenic signaling pathways, and that-outside secondary lymphoid tissues-clonal evolution is retarded by diminished BCR-signaling. This transferrable, antigenic-specific murine B-cell clone (TCL1-192) provides a platform to study the types and sites of antigen-BCR interactions and genetic alterations that result and may have relevance to patients.
    Proceedings of the National Academy of Sciences 04/2013; · 9.81 Impact Factor
  • Jan A. Burger, Nicholas Chiorazzi
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    ABSTRACT: B cell receptor (BCR) signaling plays an important pathogenic role in chronic lymphocytic leukemia (CLL) and B cell lymphomas, based on structural restrictions of the BCR, and BCR-dependent survival and growth of the malignant B cells. In CLL and lymphoma subtypes, ligand-independent (‘tonic’) and ligand-dependent BCR signaling have been characterized, which can involve mutations of BCR pathway components or be triggered by (auto)antigens present in the tissue microenvironment. In CLL, based on high response rates and durable remissions in early-stage clinical trials, there is rapid clinical development of inhibitors targeting BCR-associated kinases [Bruton's tyrosine kinase (BTK), phosphoinositide 3-kinase (PI3K)δ], which will change treatment paradigms in CLL and other B cell malignancies. Here, we discuss the evolution of this field, from BCR-related prognostic markers, to mechanisms of BCR activation, and targeting of BCR-associated kinases, the emerging Achilles’ heel in CLL pathogenesis.
  • Nicholas Chiorazzi, Dimitar G Efremov
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    ABSTRACT: The significant correlation between disease aggressiveness and the gene and protein structures of the B-cell receptors (BCRs) expressed on chronic lymphocytic leukemia (CLL) cells, together with the evidence for chronic activation of the BCR pathway, have led to the hypothesis that this leukemia initiates and progresses by selecting normal B lymphocytes reactive with a restricted set of (auto)antigens. A study recently published in Nature identified a novel signal-initiating interaction between the third complementary determining region of the IG heavy chain variable domain (HCDR3) and an epitope in the second framework region (FR2) that appears to be unique to CLL B cells and that calls into question the need for classical antigen binding in the activation and expansion of the leukemic cells. These findings are discussed in the context of available information about the antigen reactivity of CLL B cells and its potential role in clonal survival and drive.
    Cell Research 11/2012; · 10.53 Impact Factor
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    ABSTRACT: Background. While many prognostic markers in B-cell chronic lymphocytic leukemia provide insight into the biology of the disease, few have been demonstrated to be useful in the daily patient management. B-cell receptor signaling is a driving event in B-cell chronic lymphocytic leukemia progression and markers of B-cell receptor responsiveness have been shown to be of prognostic value. Single cell network profiling, a multiparametric flow cytometry-based assay, allows functional signaling analysis at the level of the single cell. Design and Methods. B-cell receptor signaling proteins (i.e. p-SYK, p-NF-κB p65, p-ERK, p-p38, p-JNK) were functionally characterized by single cell network profiling in samples from patients with B-cell chronic lymphocytic leukemia in an exploratory study (n=27) after stimulation with anti-IgM. Significant association of single cell network profiling data with clinical outcome (i.e. time to first treatment) as assessed by Cox regression models were then confirmed in patient samples in other two sequential independent studies, i.e. test study 1 (n=30), and test study 2 (n=37). Results. In the exploratory study, higher responsiveness of the B-cell receptor signaling proteins to anti-IgM was associated with poor clinical outcomes. Patient clustering based on signaling response was at least as powerful in discriminating different disease courses as traditional prognostic markers. In an unselected subgroup of Binet Stage A patients (n=21), increased anti-IgM-modulated p-ERK signaling was shown to be a significant, independent predictor of shorter time to first treatment. This result was independently confirmed in 2 test cohorts from distinct patient populations. Conclusions. These findings support the utility of the single cell network profiling assay in elucidating signaling perturbations with the potential for the development of a clinically useful prognostic test in patients with early stage B-cell chronic lymphocytic leukemia. These data support the clinical relevance of B-cell receptor signaling in B-cell chronic lymphocytic leukemia, and suggest a key role of ERK activation in the physiopathology of this leukemia.
    Haematologica 11/2012; · 5.94 Impact Factor
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    ABSTRACT: Clonal evolution occurs during the course of chronic lymphocytic leukemia (CLL), and based on other cancers, activation-induced deaminase (AID) could influence this process. However, this possibility has been questioned in CLL because the number of circulating AID mRNA(+) cells is exceedingly low, synthesis of AID protein by blood CLL cells has not been demonstrated, the full range of AID functions is lacking in U-CLL, which is the subset most likely to undergo disease progression, and no prospective analysis linking AID expression and disease severity has been reported. This study finds that circulating CLL cells and those within secondary lymphoid tissues can make AID mRNA and protein. This production is related to cell division because more AID mRNA was detected in recently divided cells, and AID protein was limited to the dividing fraction and was upregulated on induction of cell division. AID protein was functional because AID(+) dividing cells exhibited more dsDNA breaks, IGH class switching, and new IGHV-D-J mutations. Each of these actions was documented in U-CLL and M-CLL. Furthermore, AID associated with worse patient outcome and adverse cytogenetics. Thus, production of fully functional AID protein by U-CLL and M-CLL cells could be involved in clonal evolution of the disease.
    Blood 10/2012; · 9.78 Impact Factor
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    ABSTRACT: Although B-cell chronic lymphocytic leukemia (B-CLL) clones with unmutated IGHV genes (U-CLL) exhibit greater telomerase activity than those with mutated IGHV genes (M-CLL), the extent to which B-cell receptor (BCR) triggering contributes to telomerase up-regulation is not known. Therefore, we studied the effect of BCR stimulation on modulating telomerase activity. The multivalent BCR ligand, dextran conjugated anti-μ mAb HB57 (HB57-dex), increased telomerase activity and promoted cell survival and proliferation preferentially in U-CLL cases, whereas the PI3K/Akt inhibitor LY294002 blocked HB57-dex induced telomerase activation. Although both U-CLL and M-CLL clones exhibited similar membrane proximal signaling responses to HB57-dex, telomerase activity and cell proliferation, when inducible in M-CLL, differed. B-CLL cells stimulated using bivalent F(ab')(2) -goat anti-μ antibody (goat anti-μ) exhibited higher membrane proximal response in U-CLL than M-CLL cells, whereas telomerase activity, cell survival, and proliferation were induced to lower levels than those induced by HB57-dex. In normal B lymphocytes, HB57-dex induced less protein phosphorylation but more cell proliferation and survival than goat anti-μ. Although both anti-BCR stimuli induced comparable telomerase activity, normal CD5(+) B cells preferentially exhibited higher hTERT positivity than their CD5(-) counterparts. These findings provide an understanding of how BCR-mediated signals impact telomerase modulation in IGHV mutation-based subgroups of B-CLL and normal B cells.
    Blood 08/2012; 120(12):2438-49. · 9.78 Impact Factor
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    ABSTRACT: Resting mature human B cells undergo a dynamic process of clonal expansion, followed by clonal contraction, during an in vitro response to surrogate C3d-coated Ag and innate immune system cytokines, IL-4 and BAFF. In this study, we explore the mechanism for clonal contraction through following the time- and division-influenced expression of several pro- and anti-apoptotic proteins within CFSE-labeled cultures. Several findings, involving both human and mouse B cells, show that a mitochondria-dependent apoptotic pathway involving p53 contributes to the high activation-induced cell death (AICD) susceptibility of replicating blasts. Activated B cell clones exhibit elevated p53 protein and elevated mRNA/protein of proapoptotic molecules known to be under direct p53 transcriptional control, Bax, Bad, Puma, Bid, and procaspase 6, accompanied by reduced anti-apoptotic Bcl-2. Under these conditions, Bim levels were not increased. The finding that full-length Bid protein significantly declines in AICD-susceptible replicating blasts, whereas Bid mRNA does not, suggests that Bid is actively cleaved to short-lived, proapoptotic truncated Bid. AICD was diminished, albeit not eliminated, by p53 small interfering RNA transfection, genetic deletion of p53, or Bcl-2 overexpression. DNA damage is a likely trigger for p53-dependent AICD because susceptible lymphoblasts expressed significantly elevated levels of both phosphorylated ataxia telangiectasia mutated-Ser(1980) and phospho-H2AX-Ser(139). Deficiency in activation-induced cytosine deaminase diminishes but does not ablate murine B cell AICD, indicating that activation-induced cytosine deaminase-induced DNA damage is only in part responsible. Evidence for p53-influenced AICD during this route of T cell-independent clonal expansion raises the possibility that progeny bearing p53 mutations might undergo positive selection in peripherally inflamed tissues with elevated levels of IL-4 and BAFF.
    The Journal of Immunology 05/2012; 188(12):6093-108. · 5.52 Impact Factor
  • Preetesh Jain, Barbara Sherry, Nicholas Chiorazzi
    05/2012, Degree: PhD, Supervisor: Nicholas Chiorazzi and Barbara Sherry
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    Nicholas Chiorazzi, Kenji Itoh
    Arthritis Research & Therapy 04/2012; 1:1-1. · 4.30 Impact Factor
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    ABSTRACT: Mounting evidence indicates that grouping of chronic lymphocytic leukemia (CLL) into distinct subsets with stereotyped BCRs is functionally and prognostically relevant. However, several issues need revisiting, including the criteria for identification of BCR stereotypy and its actual frequency as well as the identification of "CLL-biased" features in BCR Ig stereotypes. To this end, we examined 7596 Ig VH (IGHV-IGHD-IGHJ) sequences from 7424 CLL patients, 3 times the size of the largest published series, with an updated version of our purpose-built clustering algorithm. We document that CLL may be subdivided into 2 distinct categories: one with stereotyped and the other with nonstereotyped BCRs, at an approximate ratio of 1:2, and provide evidence suggesting a different ontogeny for these 2 categories. We also show that subset-defining sequence patterns in CLL differ from those underlying BCR stereotypy in other B-cell malignancies. Notably, 19 major subsets contained from 20 to 213 sequences each, collectively accounting for 943 sequences or one-eighth of the cohort. Hence, this compartmentalized examination of VH sequences may pave the way toward a molecular classification of CLL with implications for targeted therapeutic interventions, applicable to a significant number of patients assigned to the same subset.
    Blood 03/2012; 119(19):4467-75. · 9.78 Impact Factor

Publication Stats

9k Citations
1,425.19 Total Impact Points


  • 2006–2014
    • The Feinstein Institute for Medical Research
      • • Center for Oncology and Cell Biology
      • • Laboratory of Experimental Rheumatology
      New York City, New York, United States
    • Azienda Ospedaliera, Cosenza
      Cosenza, Calabria, Italy
    • Teikyo University Hospital
      Edo, Tōkyō, Japan
  • 2002–2013
    • Hofstra North Shore-LIJ School of Medicine
      New York City, New York, United States
    • Weill Cornell Medical College
      New York City, New York, United States
  • 2011
    • Università degli Studi di Torino
      • Dipartimento di Scienze Cliniche e Biologiche
      Torino, Piedmont, Italy
    • Duke University Medical Center
      • Duke Human Vaccine Institute
      Durham, NC, United States
  • 2010–2011
    • Albert Einstein College of Medicine
      New York City, New York, United States
  • 1996–2011
    • Università degli Studi di Genova
      • Dipartimento di Medicina sperimentale (DIMES)
      Genova, Liguria, Italy
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
  • 2003–2006
    • North Shore-LIJ Health System
      Manhasset, New York, United States
  • 2004
    • University of California, San Diego
      San Diego, California, United States
  • 2001–2004
    • North Shore-Long Island Jewish Health System
      New York City, New York, United States
    • NYU Langone Medical Center
      • Department of Medicine
      New York City, NY, United States
  • 1998–2001
    • CRO Centro di Riferimento Oncologico di Aviano
      Aviano, Friuli Venezia Giulia, Italy
  • 2000
    • Amedeo Avogadro University of Eastern Piedmont
      Novara, Piedmont, Italy
  • 1979–1998
    • The Rockefeller University
      • • Laboratory of Molecular Genetics
      • • Laboratory of Investigative Dermatology
      New York City, NY, United States
  • 1990–1996
    • Cornell University
      • Department of Medicine
      Ithaca, NY, United States
  • 1995
    • New York University
      • Department of Medicine
      New York City, NY, United States
  • 1988
    • Philadelphia University
      Philadelphia, Pennsylvania, United States