Carlos Bueso-Ramos

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (135)850.44 Total impact

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    ABSTRACT: Bone marrow necrosis (BMN) is characterized by infarction of the medullary stroma, leading to marrow necrosis with preserved cortical bone. In reported small series, BMN in hematological malignancies is associated with poor prognosis. We sought to find the impact of BMN on clinical outcome in a relatively larger cohort of patients with acute leukemias. Overall we evaluated 1691 patients; 1051 with acute myeloid leukemia (AML) and 640 with acute lymphocytic leukemia referred to our institution between 2002 and 2013. Patients with AML and ALL were evaluated separately to determine the incidence of BMN, associated clinical features and its prognostic significance. At initial diagnosis; BMN was observed in 25 (2.4%) patients with AML and 20 (3.2%) patients with ALL. In AML, BMN was significantly associated with FAB AML M5 morphology (32% vs 10%, p = 0.002). The complete remission (CR) rate in AML with and without BMN was 32% and 59% respectively (p = 0.008). Likewise, CR rate in ALL with BMN was also inferior; 70% vs 92% (p = 0.005). The median overall survival (OS) in AML with BMN was significantly poorer; 3.7 months compared to 14 months without BMN (p= 0.003). Similarly, the median OS in ALL with and without BMN was 61.7 and 72 months respectively (p = 0.33). BMN is not a rare entity in AML and ALL, but is infrequent. BMN in AML and in ALL is suggestive of inferior response and poor prognosis. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    American Journal of Hematology 05/2015; DOI:10.1002/ajh.24074 · 3.48 Impact Factor
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    ABSTRACT: Myelodysplastic syndrome (MDS) risk correlates with advancing age, therapy-induced DNA damage, and/or shorter telomeres, but whether telomere erosion directly induces MDS is unknown. Here, we provide the genetic evidence that telomere dysfunction-induced DNA damage drives classical MDS phenotypes and alters common myeloid progenitor (CMP) differentiation by repressing the expression of mRNA splicing/processing genes, including SRSF2. RNA-seq analyses of telomere dysfunctional CMP identified aberrantly spliced transcripts linked to pathways relevant to MDS pathogenesis such as genome stability, DNA repair, chromatin remodeling, and histone modification, which are also enriched in mouse CMP haploinsufficient for SRSF2 and in CD34(+) CMML patient cells harboring SRSF2 mutation. Together, our studies establish an intimate link across telomere biology, aberrant RNA splicing, and myeloid progenitor differentiation. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cancer cell 05/2015; 27(5):644-657. DOI:10.1016/j.ccell.2015.04.007 · 23.89 Impact Factor
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    ABSTRACT: Histone deacetylase (HDAC) inhibitors are well-characterized anti-leukemia agents, and HDAC gene expression deregulation has been reported in various types of cancers. We sought to characterize HDAC gene expression patterns in several types of leukemia. To do so, we performed a systematic study of the mRNA expression of all drug-targetable HDACs for which reagents were available. This was done by real-time PCR in 24 leukemia cell lines and 39 leukemia patients, which included AML, MDS, and CLL patients, some of whom received HDAC inhibitor treatment. Among the samples analyzed, there was no discernible pattern in HDAC expression. HDAC expression was generally increased in CLL patients, except for HDAC2 and HDAC4. HDAC expression was also generally increased in VPA-treated MOLT4 cells. However, this increased expression was not seen in AML patients treated with vorinostat. In summary, we noted increased HDAC expression in CLL patients in general, but the HDAC expression patterns in myeloid malignancies appears to be heterogeneous, which implies that the role of HDACs in leukemia may be related to global expression or protein function rather than specific expression patterns.
    Leukemia & lymphoma 05/2015; DOI:10.3109/10428194.2015.1034705 · 2.89 Impact Factor
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    ABSTRACT: Background Progression of chronic myelogenous leukemia (CML) is frequently accompanied by cytogenetic evolution, commonly unbalanced chromosomal changes, such as an extra copy of Philadelphia chromosome (Ph), +8, and i(17)(q10). Balanced chromosomal translocations typically found in de novo acute myeloid leukemia occur occasionally in CML, such as inv(3)/t(3;3), t(8;21), t(15;17), and inv(16). Translocations involving the 11q23, a relatively common genetic abnormality in acute leukemia, have been seldom reported in CML. In this study, we explored the prevalence and prognostic role of 11q23 in CML. Methods We searched our pathology archives for CML cases diagnosed in our institution from 1998 to present. Cases with 11q23 rearrangements were retrieved. The corresponding clinicopathological data were reviewed. Results A total of 2,012 cases of CML with available karyotypes were identified. Ten (0.5%) CML cases had 11q23 rearrangement in Ph-positive cells, including 4 cases of t(9;11), 2 cases of t(11;19), and 1 case each of t(2;11), t(4;11), t(6;11), and t(4;9;11). Eight cases (80%) had other concurrent chromosomal abnormalities. There were 6 men and 4 women with a median age of 50 years (range, 21–70 years) at time of initial diagnosis of CML. 11q23 rearrangement occurred after a median period of 12.5 months (range, 0–172 months): 1 patient in chronic phase, 2 in accelerated phase, and 7 in blast phase. Eight of ten patients died after a median follow-up of 16.5 months (range, 8–186 months) following the initial diagnosis of CML, and a median of 6.7 months (range, 0.8–16.6 months) after the emergence of 11q23 rearrangement. The remaining two patients had complete remission at the last follow-up, 50.2 and 6.9 months, respectively. In addition, we also identified a case with 11q23/t(11;17) in Ph-negative cells in a patient with a history of CML. MLL involvement was tested by fluorescence in situ hybridization in 10 cases, and 7 cases (70%) were positive. Conclusions In summary, chromosomal rearrangements involving 11q23 are rare in CML, frequently occurring in blast phase, and are often associated with other cytogenetic abnormalities. These patients had a low response rate to tyrosine kinase inhibitors and a poor prognosis.
    Journal of Hematology & Oncology 04/2015; 8(1). DOI:10.1186/s13045-015-0128-2 · 4.93 Impact Factor
  • M. Shah · R. Redis · L. Fabris · C. Ivan · M. Gagea · R. Fodde · C. Bueso-Ramos · G. Garcia-Manero · G. Calin
    Leukemia Research 04/2015; 39:S33-S34. DOI:10.1016/S0145-2126(15)30069-2 · 2.69 Impact Factor
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    ABSTRACT: The interleukin-11 receptor (IL-11R) is an established molecular target in primary tumors of bone, such as osteosarcoma, and in secondary bone metastases from solid tumors such as prostate cancer. However, its potential role in management of hematopoietic malignancies has not yet been determined. Here we evaluated the IL-11R as a candidate therapeutic target in human leukemia and lymphoma. First, we show that the IL-11R protein is expressed in a variety of human leukemia- and lymphoma derived cell lines and in a large panel of bone marrow samples from leukemia and lymphoma patients, while expression is absent from non-malignant control bone marrow. Moreover, a targeted peptidomimetic prototype (termed BMTP-11) specifically bound to leukemia and lymphoma cell membranes, induced ligand-receptor internalization mediated by the IL-11R, and resulted in a specific dose-dependent cell death induction in these cells. Finally, a pilot drug lead-optimization program yielded a new myristoylated BMTP-11 analog with an apparent improved anti-leukemia cell profile. These results indicate (i) that the IL-11R is a suitable cell surface target for ligand-directed applications in human leukemia and lymphoma and (ii) that BMTP-11 and its derivatives have translational potential against this group of malignant diseases. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 03/2015; DOI:10.1158/1078-0432.CCR-13-3059 · 8.19 Impact Factor
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    ABSTRACT: While reviewing chronic lymphocytic leukemia (CLL) bone marrow slides we identified cytoplasmic lipid vacuoles in CLL cells but not in normal B cells. Because lipoprotein lipase (LPL), which catalyzes hydrolysis of triglycerides into free fatty acids (FFAs), is aberrantly expressed in CLL, we investigated whether LPL regulates the oxidative metabolic capacity of CLL cells. We found that unlike normal B cells, CLL cells metabolize FFAs. Because STAT3 is constitutively activated in CLL cells and because we identified putative STAT3 binding sites in the LPL promoter, we sought to determine whether STAT3 drives the aberrant expression of LPL. Transfection of luciferase reporter gene constructs driven by LPL promoter fragments into MM1 cells revealed that STAT3 activates the LPL promoter. In addition, chromatin immunoprecipitation (ChIP) confirmed that STAT3 binds to the LPL promoter. Furthermore, transfection of CLL cells with STAT3-shRNA downregulated LPL transcripts and protein levels, confirming that STAT3 activates the LPL gene. Finally, transfection of CLL cells with LPL-siRNAs decreased the capacity of CLL cells to oxidize FFAs and reduced cell viability. Implications: Our study suggests that CLL cells adopt their metabolism to oxidize FFA. Activated STAT3 induces LPL, which catalyzes the hydrolysis of triglycerides into FFA. Therefore, inhibition of STAT3 is likely to prevent the capacity of CLL cells to utilize FFA. Copyright © 2015, American Association for Cancer Research.
    Molecular Cancer Research 03/2015; 13(5). DOI:10.1158/1541-7786.MCR-14-0412 · 4.50 Impact Factor
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    ABSTRACT: We previously demonstrated vast expansion of hypoxic areas in the leukemic microenvironment and provided rationale for using hypoxia-activated prodrugs. PR104 is a phosphate ester that is rapidly hydrolyzed in vivo to the corresponding alcohol PR-104A and further reduced to the amine and hydroxyl-amine nitrogen mustards that induce DNA cross-linking in hypoxic cells under low oxygen concentrations. In this phase I/II study, patients with relapsed/refractory acute myeloid leukemia (n=40) after 1 or 2 prior treatments or acute lymphoblastic leukemia (n=10) after any number of prior treatments received PR104, dose ranges of 1.1 to 4 g/m2. The most common treatment-related grade 3/4 adverse events were myelosuppression (anemia 62%, neutropenia 50%, thrombocytopenia 46%), febrile neutropenia (40%), infection (24%), and enterocolitis (14%). Ten of 31 patients with acute myeloid leukemia (32%) and 2 of 10 patients with acute lymphoblastic leukemia (20%) who received 3 g/m2 or 4 g/m2 had a response (complete response, n=1; complete response without platelet recovery, n=5; morphologic leukemia-free state, n=6). The extent of hypoxia was evaluated by the hypoxia tracer pimonidazole administered prior to a bone marrow biopsy and by immunohistochemical assessments of hypoxia-inducible factor alpha and carbonic anhydrase IX. A high fraction of leukemic cells expressed these markers, and PR104 administration resulted in measurable decrease of the proportions of hypoxic cells. These findings indicate that hypoxia is a prevalent feature of the leukemic microenvironment and that targeting hypoxia with hypoxia-activated prodrugs warrants further evaluation in acute leukemia. The trial is registered at ClinicalTrials.gov as NCT 01037556. Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 02/2015; 100(7). DOI:10.3324/haematol.2014.118455 · 5.87 Impact Factor
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    ABSTRACT: Correlative and functional studies support the involvement of the RUNX gene family in haematological malignancies. To elucidate the role of epigenetics in RUNX inactivation, we evaluated promoter DNA methylation of RUNX1, 2, and 3 in 23 leukaemia cell lines and samples from acute myeloid leukaemia (AML), acute lymphocytic leukaemia (ALL) and myelodysplatic syndromes (MDS) patients. RUNX1 and RUNX2 gene promoters were mostly unmethylated in cell lines and clinical samples. Hypermethylation of RUNX3 was frequent among cell lines (74%) and highly variable among patient samples, with clear association to cytogenetic status. High frequency of RUNX3 hypermethylation (85% of the 20 studied cases) was found in AML patients with inv(16)(p13.1q22) compared to other AML subtypes (31% of the other 49 cases). RUNX3 hypermethylation was also frequent in ALL (100% of the six cases) but low in MDS (21%). In support of a functional role, hypermethylation of RUNX3 was correlated with low levels of protein, and treatment of cell lines with the DNA demethylating agent, decitabine, resulted in mRNA re-expression. Furthermore, relapse-free survival of non-inv(16)(p13.1q22) AML patients without RUNX3 methylation was significantly better (P = 0·016) than that of methylated cases. These results suggest that RUNX3 silencing is an important event in inv(16)(p13.1q22) leukaemias. © 2015 John Wiley & Sons Ltd.
    British Journal of Haematology 01/2015; 169(3). DOI:10.1111/bjh.13299 · 4.96 Impact Factor
  • 01/2015; 2(1):e12-e20. DOI:10.1016/S2352-3026(14)00026-X
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    ABSTRACT: Background De novo acute myeloid leukemia (AML) with concurrent DNMT3A, FLT3 and NPM1 mutations (AML DNMT3A/FLT3/NPM1 ) has been suggested to represent a unique AML subset on the basis of integrative genomic analysis, but the clinical features of such patients have not been characterized systematically. Methods We assessed the features of patients (n¿=¿178) harboring mutations in DNMT3A, FLT3 and/or NPM1, including an index group of AML DNMT3A/FLT3/NPM1 patients.ResultsPatients with AML DNMT3A/FLT3/NPM1 (n¿=¿35) were significantly younger (median, 56.0 vs. 62.0 years; p¿=¿0.025), mostly women (65.7% vs. 46.9%; p¿=¿0.045), and presented with a higher percentage of bone marrow blasts (p¿<¿0.001) and normal cytogenetics (p¿=¿0.024) in comparison to other groups in this study. Among patients <60 years old, those with AML DNMT3A/FLT3/NPM1 had a shorter event-free survival (EFS) (p¿=¿0.047). DNMT3A mutations and not FLT3 or NPM1 mutations were independently associated with overall survival (OS) (p¿=¿0.026). Within mutation subgroups, patients with AML DNMT3A/NPM1 had a significantly shorter OS compared to those with AML FLT3-ITD/NPM1 (p¿=¿0.047) suggesting that the adverse impact of DNMT3A mutations is more pronounced than that of FLT3-ITD among patients with NPM1 mutation.ConclusionsDNMT3A has a significant effect on the clinical features and outcomes of de novo AML patients with concurrent DNMT3A, FLT3 and NPM1 mutations.
    Journal of Hematology & Oncology 10/2014; 7(1):74. DOI:10.1186/s13045-014-0074-4 · 4.93 Impact Factor
  • Clinical Lymphoma, Myeloma and Leukemia 09/2014; 14:S134. DOI:10.1016/j.clml.2014.06.064 · 2.02 Impact Factor
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    ABSTRACT: Follicular lymphoma in situ is a rare, recently described entity. It is defined by the accumulation of t(14;18)+, BCL2 strongly positive clonal B cells restricted to germinal centers in morphologically normal lymph nodes, without alteration of follicle morphology, size or distribution, or perifollicular spread. The presence of a follicular lymphoma in situ has three main clinical ramifications, including the potential coexistence of a simultaneous disseminated follicular lymphoma, risk of subsequent overt follicular lymphoma, and association with a second subtype of lymphoma. We report cases of follicular lymphoma in situ in conjunction with lymphoplasmacytic lymphoma (two cases) and mantle cell lymphoma (one case). Each case was evaluated, and diagnoses confirmed using a combination of histologic, immunohistochemical, fluorescence in situ hybridization (FISH), and molecular techniques. One case of lymphoplasmacytic lymphoma was proven positive for myeloid differentiation primary response 88 gene (MYD88) mutation. Our series expands the current literature of this rare phenomenon. We discuss possible etiologies and clinical impact of follicular lymphoma in situ.
    09/2014; 7(3):95-101. DOI:10.1007/s12308-014-0212-5
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    ABSTRACT: t(10;11)(p12;q23) is a rare recurrent translocation involving the mixed lineage leukemia (MLL) gene translocation, most commonly seen in pediatric and young adult acute myeloid leukemia (AML), associated with early morbidity including diffuse intravascular coagulation and tumor lysis syndrome with multiorgan system failure from leukocytosis. With supportive care, first remissions are frequently attained, but patients have a high risk of relapse, extramedullary disease, and poor long-term outcomes. Introduction: Acute myeloid leukemias with MLL rearrangements are frequently associated with myelomonocytic and monoblastic/monocytic morphology, with an increased risk of leukocytosis and leukostasis-related complications. Yet, little is known regarding the clinical presentation of adult AML patients with MLL translocations based on the specific translocation partner. Patients and Methods: Two recent AML cases with t(10;11)(p12;q23) translocations are detailed, with their shared presenting symptoms highlighted, followed by a review of the current literature. Results: The specific t(10;11)(p12;q23) MLL translocation is a rare recurrent translocation partner, most commonly seen in pediatric and young adult AML. A high incidence of early morbidity from leukocytosis-related complications are frequently seen, including diffuse intravascular coagulation and tumor lysis syndrome with multiorgan system failure, even without a true leukocytosis. Conclusion: With prompt therapy and intensive supportive care first remissions are frequently attained, however, patients have a high risk of relapse, extramedullary disease, and poor long-term outcomes.
    Clinical Lymphoma, Myeloma and Leukemia 06/2014; 15(1). DOI:10.1016/j.clml.2014.06.022 · 2.02 Impact Factor
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    ABSTRACT: Here it was determined that Chronic Lymphocytic Leukemia (CLL) cells express the alpha-subunit but not the beta-subunit of the granulocyte-macrophage colony-stimulating factor receptor (GMCSFR/CSF3R). GM-CSFRalpha was detected on the surface, in the cytosol, and the nucleus of CLL cells via confocal microscopy, cell fractionation, and GM-CSFRalpha antibody epitope mapping. Because STAT3 is frequently activated in CLL and the GM-CSFRalpha promoter harbors putative STAT3 consensus binding sites, MM1 cells were transfected with truncated forms of the GMCSFRalpha promoter, then stimulated with IL-6 to activate STAT3 to identify STAT3 binding sites. Chromatin immunoprecipitation (ChIP) and an electoromobility shift assay (EMSA) confirmed STAT3 occupancy to those promoter regions in both IL-6 stimulated MM1 and CLL cells. Transfection of MM1 cells with STAT3 siRNA or CLL cells with STAT3 shRNA significantly downregulated GM-CSFRalpha mRNA and protein levels. RNA transcripts, involved in regulating cell survival pathways, and the proteins KAP1 (TRIM28) and ISG15 co-immunoprecipitated with GMCSFRalpha. GM-CSFRalpha-bound KAP1 enhanced the transcriptional activity of STAT3, whereas ISG15 inhibited the NF-kappaB pathway. Nevertheless, overexpression of GM-CSFRalpha protected MM1 cells from dexamethasone-induced apoptosis, and GM-CSFRalpha knockdown induced apoptosis in CLL cells, suggesting that GM-CSFRalpha provides a ligand-independent survival advantage. Implications: Constitutively activate STAT3 induces the expression of GM-CSFRalpha and protects CLL cells from apoptosis, suggesting that inhibition of STAT3 or GM-CSFRalpha may benefit patients with CLL.
    Molecular Cancer Research 05/2014; 12(9). DOI:10.1158/1541-7786.MCR-13-0652-T · 4.50 Impact Factor
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    ABSTRACT: Background: Comorbidities significantly affect the prognosis and outcomes of patients with hematological malignancies. We have previously reported the impact of comorbidities on the IPSS score. The aim of this study was to determine whether comorbidities continued to have a significant impact when patients were reclassified according to the Revised-International Prognostic Scoring System (IPSS-R). Methods: The medical records of 600 consecutive MDS patients who presented to MD Anderson Cancer Center between January 2002 and June 2004 were reviewed. The Adult Comorbidity Evaluation-27 (ACE-27) was used to assess the severity of comorbid conditions. Results: Four hundred and two (67%) patients were male. Median age at presentation was 66.6 years (17 - 94). Mean duration of follow-up was 54 months (1 - 100). Five hundred and two (84%) patients died, and 54 (9%) patients underwent SCT. Overall median survival was 16.8 months (1 - 100). Median survival by IPSS-R was 47, 34, 21, 16, and 6 months for patients in very low, low, intermediate, high and very high-risk groups, respectively (P<0.001). The ACE-27 comorbidity score significantly impacted the median survival of patients in the intermediate (P<0.001), high (P=0.045), and very high (P=0.004) IPSS-R groups; but did not significantly impact the median survival in the low (P=0.11) and very low (P=0.49) IPSS-R groups. The ACE-27 comorbidity score significantly impacted the median survival of patients ≤ 65 years (P<0.001) but did not significantly impact those > 65 years (P=0.18). Conclusion: Assessment of comorbidity may enhance the prognostic ability of the IPSS-R.
    American Journal of Hematology 05/2014; 89(5). DOI:10.1002/ajh.23675 · 3.48 Impact Factor
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    ABSTRACT: Myelodysplastic syndromes (MDS) are characterized by impaired proliferation and differentiation of hematopoietic stem cells. The participation of toll-like receptor (TLR)-mediated signaling in MDS is well documented. Increased TLR signaling leads to the constitutive activation of NF-κB, which mediates inflammation, cell proliferation and apoptosis. In addition, the TLR pathway induces the expression of miRNAs which participate in the fine-tuning of the inflammatory response. miRNAs also regulate other biological processes, including hematopoiesis. miR-125a and miR-125b are known modulators of hematopoiesis and are abnormally expressed in several hematologic malignancies. However, little is known about their role in MDS. NF-κB-activating ability has been described for both miRNAs. We studied the role of miR-125a/miR-125b in MDS and their relationship with TLR signaling and hematopoietic differentiation. Our results indicate that miR-125a is significantly overexpressed in MDS patients and correlates negatively with patient survival. Expression of miR-99b, which is clustered with miR-125a, is also directly correlated with prognosis of MDS. Both miR-125a and miR-99b activated NF-κB in vitro; however, we observed a negative correlation between miR-99b expression and the levels of TLR2, TLR7 and two downstream genes, suggesting that NF-κB activation by the miRNA cluster occurs in the absence of TLR signaling. We also show that TLR7 is negatively correlated with patient survival in MDS. In addition, our data suggest that miR-125a may act as an NF-κB inhibitor upon TLR stimulation. These results indicate that miR-125a is involved in the fine-tuning of NF-κB activity and that its effects may depend on the status of the TLR pathway. Furthermore, we observed that miR-125a inhibits erythroid differentiation in leukemia and MDS cell lines. Therefore, this miRNA could serve as a prognostic marker and a potential therapeutic target in MDS.
    PLoS ONE 04/2014; 9(4):e93404. DOI:10.1371/journal.pone.0093404 · 3.23 Impact Factor
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    ABSTRACT: Atypical chronic myeloid leukemia (aCML) is a rare subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) largely defined morphologically. It's, unclear, however, whether aCML associated features are distinctive enough to allow its separation from unclassifiable MDS/MPN (MDS/MPN-U). To study these two rare entities, 134 patient archives were collected from 7 large medical centers, of which, 65 (49%) cases were further classified as aCML and the remaining 69 (51%) MDS/MPN-U. Distinctively, aCML was associated with many adverse features and an inferior overall survival (12.4 vs.21.8 months, p=0.004) and AML free survival (11.2 vs.18.9 months, p=0.003). The aCML defining features as of leukocytosis and circulating myeloid precursors, but not dysgranulopoiesis, were independent negative predictors. Other factors, such as LDH, circulating myeloblasts, platelets, and cytogenetics could further stratify MDS/MPN-U but not aCML patient risks. aCML appeared to have more mutated RAS [7/20(35%) vs.4/29(14%)] and less JAK2p.V617F [3/42(7%) vs.10/52(19%)]; but not statistically significant. Somatic CSF3R T618I(0/54) and CALR (0/30) mutations were not detected either in aCML or MDS/MPN-U. In conclusion, within the MDS/MPN, the WHO 2008 criteria for aCML identify a subgroup of patients with features clearly distinct from MDS/MPN-U. The MDS/MPN-U category is heterogeneous, and patient risk can be further stratified by a number of clinicopathological parameters.
    Blood 03/2014; 123(17). DOI:10.1182/blood-2014-02-553800 · 10.43 Impact Factor
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    ABSTRACT: Purpose Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is a variant of DLBCL with worse outcome that occurs most often in East Asian countries and is uncommon in the Western hemisphere. We studied the largest cohort of EBV+ DLBCL, independent of age, treated with R-CHOP in developed Western countries. Experimental design A large cohort (n=732) of patients with DLBCL treated with R-CHOP chemotherapy are included from the multicenter Consortium. This study group has been studied for expression of different biomarkers by immunohistochemistry, genetic abnormalities by fluorescent in situ hybridization and mutation analysis, genomic information by gene expression profiling (GEP) and gene set enrichment analysis (GSEA). Results Twenty-eight patients (4.0%) were positive for EBV with a median age of 60.5 years. No clinical characteristics distinguished patients with EBV+ DLBCL from patients with EBV-negative DLBCL. Genetic aberrations were rarely seen. NF-κB p50, phosphorylated STAT-3 and CD30 were more commonly expressed in EBV+ DLBCLs (P<.05). Significant differences in survival were not observed in patients with EBV-positive DLBCL versus EBV-negative DLBCL. CD30 co-expression appeared to confer inferior outcome although statistical significance was not achieved. GEP showed a unique expression signature in EBV-positive DLBCL. GSEA revealed enhanced activity of the NF-κB and JAK/STAT pathways. Conclusions The clinical characteristics of patients with EBV+ versus EBV-negative DLBCL are similar and EBV infection does not predict a worse outcome. EBV+ DLBCL, however, has a unique genetic signature. CD30 expression is more common in EBV+ DLBCL and, when present, is associated with an adverse outcome.
    Clinical Cancer Research 02/2014; 20(9). DOI:10.1158/1078-0432.CCR-13-3157 · 8.19 Impact Factor

Publication Stats

5k Citations
850.44 Total Impact Points

Institutions

  • 1998–2015
    • University of Texas MD Anderson Cancer Center
      • • Department of Hematopathology
      • • Department of Leukemia
      • • Department of Pathology
      Houston, Texas, United States
  • 2013
    • University of Texas at Austin
      Austin, Texas, United States
  • 2001–2005
    • University of Houston
      Houston, Texas, United States