At the 54th Annual Meeting of the American Society of Hematology (ASH), held in Atlanta, nearly 5,000 abstracts were presented in oral sessions and posters. As part of our ongoing comprehensive coverage from the meeting, here are several more studies of note.
New Targets in Acute Myeloid Leukemia
Anupriya Agarwal, PhD,and colleagues from the Oregon Health & Science University and Howard Hughes Medical Institute in Portland used a novel RNA interference (RNAi) screen to identify nonkinase cytokine and growth factor receptors involved in leukemogenesis.1 In screening for 188 growth factor receptors highly expressed in gene microarray analysis of primary acute myeloid leukemia (AML) patient specimens, candidate targets identified in AML patient samples included CD24, NCOA4, IL2Rα, IL15Rα, and IL2Rγ. These targets were often found to have genetic abnormalitiesranging from splice variation (IL2Rα) to intron retention (IL15Rα), and in some cases, the receptors were found to contribute to oncogenesis by acting as a scaffold for regulating downstream oncogenic signaling.
Additional study of IL2Rγ showed the receptor to be essential for JAK3 mutant-mediated leukemogenesis. Knockdown of IL2Rγ significantly reduced the viability of JAK3 A572V mutant cells (CMK cell line; 90% decrease) and blocked phosphorylation of JAK3 and the downstream signaling molecules STAT5, MAPK, and pS6 ribosomal protein. Overexpression of IL2Rγ enhanced JAK3 A572V-mediated signaling, increased its transformation potential in a ligand-independent manner, increased the oncogenic potential of other JAK3 mutants identified in AML patients, and reduced sensitivity of JAK3 A572V cells to a JAK family inhibitor. Further, the absence of IL2Rγ in murine bone marrow completely blocked the clonogenic potential of JAK3 A572V compared with IL2Rγ-wild type marrow. IL2Rγ was found to contribute to constitutive JAK3 mutant signaling by increasing JAK3 protein levels and phosphorylation; mutant but not wild-type JAK3 was shown to increase expression of IL2Rγ, indicating that IL2Rγ contributes to constitutive JAK3 signaling through a feedback mechanism.
“RNAi-based functional screening for AML cell dependence on non-kinase cytokine and growth factor receptors led to the identification of novel oncogenic etiologies for AML. These findings underscore the importance of cytokine and growth factor receptors in leukemia pathogenesis,” the investigators noted.
They continued, “This assay can identify genes that are crucial for malignant cell growth, regardless of the mutational status, both incell lines and in primary samples. Future studies integrating this RNAi screen with deep sequencing will lend additional power to this assay by accelerating our understanding of the genetic mechanisms underlying these functional gene targets such that these findings can be rapidly translated into novel therapeutic strategies.”
Overcoming Chemoresistance in Aggressive B-cell Lymphomas
Increased glucose metabolism and continuous reactive oxygen species (ROS) production is a metabolic adaptation strategy of tumor cells that relieves the stress caused by lack of nutrients and oxygen in the tumor environment. Thioredoxin interacting protein (TXNIP) is a negative regulator for both redox thioredoxin (ROS production) and cellular glucose uptake that is found to be repressed in various cancers, including diffuse large B-cell lymphomas. Recent studies have identified frequent mutations in the gene for EZH2 (a highly conserved histone methyltransferase) that lead to critical gene silencing in diffuse large B-cell lymphoma pathophysiology.
Kejie Zhang, MD, PhD, and colleagues from Xiamen University, China, and The University of Texas MD Anderson Cancer Center in Houston showed that (1) EZH2 is either overexpressed or mutated in representative diffuse large B-cell lymphoma cell lines and primary lymphoma cells, (2) downregulation of EZH2 with siRNA leads to the reactivation of TXNIP with subsequent inhibition of tumor cell growth and survival mediated through both thioredoxin (ROS) and glucose metabolism in diffuse large B-cell lymphomas, and (3) histone deacetylation is also involved in EZH2-mediated silencing of TXNIP in diffuse large B-cell lymphomas.2
The histone methylation inhibitor DZNep was shown to be highly effective in inhibiting cell growth in diffuse large B-cell lymphoma lines, particularly chemoresistant lines, and DZNep and the histone deacetylation inhibitor vorinostat (Zolinza) showed synergistic activity in reactivating TXNIP gene expression and inhibiting diffuse large B-cell lymphoma cell growth and survival. The investigators also found that EZH2 regulates constitutive NF-κB activity through both canonical and alternative NF-κB pathways in diffuse large B-cell lymphomas independent of its histone methyltransferase activity, with the findings indicating that the two oncogenic factors exhibit functional crosstalk in lymphoma cells.
The investigators concluded, “Our findings have indicated that deregulated EZH2 leads to constitutive NF-κB activation and to epigenetic silencing of TXNIP, resulting in uncontrolled tumor cell growth and survival mediated through both thioredoxin and glucose metabolism in [diffuse large B-cell lymphomas], and that targeting this pathway represents a novel, rational, and effective therapeutic approach to selectively reverse chemoresistance in [diffuse large B-cell lymphoma] patients, particularly relapsed/refractory patients.”
Role of Mutations in Childhood Myelodysplastic Syndrome
Researchers from institutions in 11 European nations examined the occurrence of genetic aberrations in an international cohort of 107 pediatric myelodysplastic syndrome (MDS) patients to determine the potential collaborative roles of mutations associated with hyperproliferation (type I) and maturation arrest (type II), reported Andrica de Vries, MD, of Sophia Children’s Hospital, Rotterdam, Netherlands, and colleagues at the ASH meeting.3 Forty-four patients had primary de novo MDS, and 63 had secondary MDS. Karyotypes were studied and the hotspot regions of the NPM1, CEPBA, FLT3, N-RAS, K-RAS, BRAF, PTPN11, c-KIT, RUNX1, P53, ASXL1, NUP98, IDH1 and 2, DNMT3A,and TET2 geneswere screened for mutations.
Type I aberrations were found in 8 patients (7%), including 4 of those (9%) with primary MDS and 4 (6%) of those with secondary MDS. Mutations were found in FLT3–ITD in 3 patients, N-RAS in 2, K-RAS in 2, and PTPN11 in 1. No mutations were found in FLT3-TKD, c-KIT, P53,or BRAF.
Type II aberrations were found in 17 patients (16%), including 4 (9%) of those with primary MDS and 13 (21%) of those with secondary MDS. Aberrations included MLL rearrangements in 2 patients, RUNX1 rearrangement in 1, RUNX1 mutations in 7, duplications in CEBPα in 5, NPM1 mutations in 1, and NUP98 translocation in 1.
Overall, ASXL1 mutations were found in 2 patients and DNMT3A mutations in 1, but no TET2, IDH1, or IDH2 mutationswere found in any of the patients. Collaborative type I and II mutations were found in only 2 patients (NRAS + RUNX1 mutation and ASXL1 + RUNX1 mutation), both with secondary MDS.
The investigators concluded, “This studyindicates that in childhood MDS, in contrast to adult MDS, the currently known molecular aberrations, especially the histone modifying and DNA methylating-influencing aberrations, are of minor importance in the pathogenesis of childhood MDS.”
Markers for p53 Deficiency and Outcome in Diffuse Large B-cell Lymphoma
Diffuse large B-cell lymphoma is a clinically and biologically heterogeneous disease characterized by a high proliferation rate and infrequent somatic mutations of TP53 and genes for cell-cycle pathway components. Bjoern Chapuy, MD, PhD, and colleagues from Dana-Farber Cancer Institute and Harvard Medical School in Boston, Broad Institute of Harvard University and Massachusetts Institute of Technology in Cambridge, and Mayo Clinic in Rochester, Minnesota, identified a comprehensive set of copy number alterations associated with decreased p53 activity and perturbed cell-cycle regulation and found that ‘complex’ vs ‘clean’ patterns of occurrence of copy number alterations were associated with survival outcome in diffuse large B-cell lymphoma.4
Primary diffuse large B-cell lymphoma tumors with single copy loss of 17p13.1 (TP53/RPL26/KDM6B) often had copy number alterations of an additional p53 modifier—eg, 9p21.3 (CDKN2A/ARF), 19q13.42 (BCL2L12), 12q15 (MDM2) or 1q23.3 (MDM4/RFWD2). Copy number alterations of some of the modifiers occurred in largely distinct groups of tumors. Tumors with copy number alterations in p53 pathway members also frequently exhibited concurrent alterations of other cell-cycle components, including CCND3 (6p21.32), CDK6 (7q22.1), CDK2/CDK4 (12q15), and RB1 (13q14.2) or RBL2 (16q12.2).
When the primary diffuse large B-cell lymphoma tumors were analyzed according to presence of copy number alterations that perturb the p53 pathway and cell-cycle components, 66% of tumors had multiple alterations (“complex” pattern) and the remaining 34% of tumors lacked these lesions (“clean” signature). Tumors with the “complex” pattern also had more total copy number alterations and more frequent TP53 mutations, highlighting the association among p53 deficiency, cell cycle deregulation, and increased genomic instability in diffuse large B-cell lymphoma. “Complex” tumors had lower levels of p53 transcripts, linking the genetic signature of p53 deficiency with decreased p53 activity, and significantly higher proliferation indices.
Analysis of outcomes in patients who had received R-CHOP therapy (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) and had long-term follow up showed a 5-year overall survival of 62% in patients with “complex” copy number alteration patterns and 100% in those with “clean” copy number alteration signatures (P = .001). The association between copy number alteration complexity and survival outcome was independent of transcriptionally defined categories and additive to International Prognostic Index risk assessment.
The investigators concluded, “Taken together, these data provide a structural basis for deregulated cell cycle, increased cellular proliferation and unfavorable outcome in [diffuse large B-cell lymphoma] and suggest targeted treatment strategies.”
AML Bone Marrow Microenvironment Impairs Dendritic Cell Maturation and Antigen Presentation
The bone marrow stroma interacts with cancer cells in a manner that supports blocking of apoptosis, resistance to chemotherapy, and suppression of antitumor immune mechanisms. Bettina Wagner, MD, and colleagues from University Hospital Essen and InSCREENeX GmbH in Braunschweig, Germany, investigated the effects of cellular factors in bone marrow stromal cells from AML patients on maturation of dendritic cells.5
Dendritic cell maturation in the presence and absence of stromal cell fragments (using surface markers including CD40, CD80, CD83, CD86, and CD274) were investigated before maturation on monocytes, after the addition of stromal fragments on day 3, and on terminally differentiated dendritic cells on day 7, and the expression of classical (HLA class I, HLA-DR) and nonclassical (HLA-G, HLA-E) immunoregulatory molecules was measured. Terminal differentiation of dendritic cells was promoted by the addition of proinflammatory cytokines (IL-4, GM-CSF, IL-1β, and TNFα).
A marked decrease in expression of differentiation (up to 36% reduction) and antigen presentation (up to 68% reduction) molecules of dendritic cells cultured in the presence of AML marrow stromal cell fragments was observed compared to maturation without AML stromal cell fragments. A decrease in HLA-DR expression was not restored by the addition of the proinflammatory cytokines at day 7, and the reduction in HLA-DR expression with the addition of AML stromal cell fragments was greater than that observed with the addition of fragments from healthy donor cells. The investigators concluded that the findings “indicate that molecules derived from the AML stroma cells are implicated in mechanisms impairing [dendritic cell] maturation and function, which may promote immune escape during leukemia development.”
Cyclophosphamide-induced Cytokine Release Sensitizes Tumor Microenvironment to Antibody-mediated Therapy
In studies in the hMB humanized lymphoma mouse model and CD20+ B-ALL xenograft mice, Christian P. Pallasch, MD, and colleagues from Massachusetts Institute of Technology, Cambridge, University of Cologne, Germany, Vrije University Medical Centre in Amsterdam, and Klinikum Schawing in Munich, Germany, showed that cyclophosphamide sensitizes the tumor microenvironment to the effects of antibody-based therapy with alemtuzumab and rituximab.6
Response to antibody therapy alone was mediated by direct phagocytosis by macrophages, with limited response seen in the bone marrow due to the resistant microenvironment in the marrow. The combination of cyclophosphamide with either of the antibodies was synergistic in producing a profound depletion of malignant cells from the bone marrow and spleen; mice receiving combination treatment survived significantly longer (median survival 7 vs 28 weeks, P < .001). Synergy with antibody therapy was not observed with other alkylating agents, topoisomerase inhibitors, spindle poisons, or steroids.
Cyclophosphamide induced an increase of F4/80+ macrophages in the primarily resistant bone marrow, and increased phagocytic activity was observed in leukemia-infiltrated and treated tumor tissue. Cyclophosphamide treatment of leukemia cells resulted in an acute secretory response that significantly enhanced macrophage-mediated cell depletion with subsequent antibody treatment. VEGF, CLL4, TNFα, and IL-8 were specifically induced by cyclophosphamide, and studies using recombinant cytokines or inhibitory antibodies also demonstrated the activity of these cytokines in enhancing macrophage-dependent leukemia cell removal.
The investigators concluded, “Here we could identify secretory phenotypes of malignant cells determining therapeutic outcome in antibody-based therapies. These findings underline the importance of tumor-microenvironment interactions for therapeutic outcome. Thus, the acute induction of stress-related cytokines represents a highly effective strategy to target cancer cells for targeted removal by the innate immune system. Here we identified so far unraveled mechanisms of synergy in chemo-immunotherapy and will thereby improve future design of clinical treatment regimens.”
Better Survival in AML Patients Over 60 with Greater Body Mass Index
AML is more common among patients over the age of 60, who have a poorer prognosis. Increased body mass index has been associated with an increased incidence of numerous malignancies, including AML. Andrew M. Brunner, MD, and colleagues from Harvard Medical School, Dana-Farber Cancer Institute, and Massachusetts General Hospital in Boston performed a retrospective analysis to determine whether patient body mass index at time of AML diagnosis is related to overall survival among patients older than age 60 years.7
Among 152 patients with AML diagnosed after the age of 60 at Massachusetts General Hospital, median age was 68 years (range, 60–87 years), 54% of patients were male, and 86% were white. Patient disease was identified as de novo in 50% and secondary in 50%. Cytogenetics were available in 86.2% of patients, and were most commonly normal (37.5%) or poor risk (34.2%), with only 1.3% of patients considered good risk.
The median overall survival for all patients was 269 days, and the 60-day overall survival was 83%. On univariate analysis, reduced overall survival was associated with increased age (P = .024), body mass index less than 27 kg/m2 (the median body mass index in the cohort; P = .011), coronary artery disease (P = .042); and cytogenetics (P = .013). On multivariable analysis, the hazard ratio (HR) for death was increased with older age (HR = 1.53, P = .027), body mass index less than 27 kg/m2 (HR = 1.93, P = .002) , and cytogenetics (P < .05); no significant associations were found between overall survival and coronary artery disease, diabetes, gender, race, de novo vs secondary disease, or presenting hematocrit, sodium, or total bilirubin.
The investigators concluded, “Patients over the age of 60 with a new diagnosis of AML carry a poor prognosis; comorbid disease at the time of presentation may assist a clinician in risk stratification of this age group. Intriguingly, [body mass index] greater than or equal to 27 was associated with improved [overall survival] among patients older than 60 treated at our institution. Additional studies will be necessary to determine the causal factors of worse survival in patients older than age 60 who have normal [body mass index] compared to obese patients and to identify approaches that will ameliorate these poorer outcomes in this population.”
Trisomy 21 Alone Portends Better Survival in AML
Congenital trisomy 21 (Down syndrome) is associated with increased risk for AML. Acquired trisomy 21 (+21) has been empirically categorized as an intermediate-risk cytogenetic abnormality in AML. However, it frequently occurs in association with other karyotypic abnormalities in AML, and its prognostic impact is poorly defined. Paolo Strati, MD, and colleagues from The University of Texas MD Anderson Cancer Center in Houston analyzed outcomes in 90 AML patients with trisomy 21 aberrations who presented to the center at diagnosis between 1995 and 2011 and who had no prior therapy.8
Four cytogenetic groups were defined: +21 alone (12% of patients), +21 plus favorable cytogenetics (8%), +21 plus intermediate cytogenetics (8%), and +21 plus unfavorable cytogenetics (72%). Induction regimens included idarubicin plus cytarabine-, fludarabine-, clofarabine-, topotecan-, and hypomethylating-based regimens.
Among all patients, the overall response rate was 54%, with clofarabine-based induction producing the highest frequency of complete remission (70%) and hypomethylating-based regimens producing the lowest (56%). The median time to complete remission in patients who achieved one was 5 weeks (range, 3–19 weeks). Patients with +21 alone and patients treated with hypomethylating-based therapy had significantly longer times to complete remission. Median duration of complete remission was 5 months (range, 1–100 months), and complete remission duration did not differ according to cytogenetic group or induction regimen.
Median progression-free survival among all patients was 11 months (range, 2–130 months), and was significantly longer among patients with +21 alone (101 months) vs the intermediate and unfavorable cytogenetics groups (11 and 2 months, respectively, P = .006). Median overall survival for the entire group was 9 months (range, 0–130 months), and was significantly longer in patients with +21 alone (32 months) than in those in the intermediate and unfavorable cytogenetics groups (5 and 2 months, respectively, P < .01). On multivariate analysis (with white blood cells, peripheral blasts, previous hematologic malignancies, performance status, age, and induction treatment as covariates), the overall survival improvement in the +21 alone group vs the intermediate and unfavorable cytogenetics groups remained significant (P < .001).
The investigators concluded, “Patients with AML harboring +21 aberrations have unique biological and clinical features. When present as a sole aberration it is associated with significantly improved [progression-free and overall survival]. Thus +21 alone may be a favorable prognostic factor in AML.”
Multiple Myeloma Marrow Infiltration Patterns in Patients with Smoldering Myeloma
Jens Hillengass, MD, and colleagues from University of Heidelberg and the German Cancer Research Center in Heidelberg, Germany, and the National Cancer Institute in Bethesda, Maryland, used whole-body MRI to characterize patterns of tumor infiltration in the bone marrow of patients diagnosed with smoldering myeloma.9 Overall, 157 patients with smoldering myeloma, 138 with monoclonal gammopathy of undetermined significance (MGUS), and 249 with multiple myeloma were assessed by whole-body MRI.
Patients with second malignancies, amyloidosis, solitary plasmocytoma, or preceding systemic treatment were excluded from the study. The endpoint for progression-free survival was initiation of systemic treatment in patients with smoldering myeloma or MGUS and relapse after systemic therapy in patients with multiple myeloma. Median follow-up was 4.5, 4.0, and 3.7 years for smoldering myeloma, MGUS, and multiple myeloma patients, respectively.
In MGUS patients, focal lesions were found in 24% and diffuse infiltration in 53%, with the patterns occurring independently from each other. The presence and number of focal lesions and the presence of severe diffuse infiltration were statistically significant adverse prognostic factors for progression-free survival; on multivariate analysis, only the number of focal lesions remained statistically significant (P = .0005). In smoldering myeloma patients, focal lesions were present in 34% and a diffuse infiltration pattern in 46%. Plasma cell percentage, a moderate diffuse infiltration (but not focal lesions), and beta2-microglobulin were significant predictors of progression-free survival.
Patterns of tumor cell infiltration in the bone marrow in smoldering myeloma patients were similar to those in MGUS patients in 66% and to those in multiple myeloma patients in 34%. There was a borderline difference in treatment-free survival between MGUS-like smoldering myeloma patients and multiple myeloma–like smoldering myeloma patients (P = .08), whereas survival was significantly increased in MGUS patients compared with multiple myeloma–like smoldering myeloma patients (P = .02).
The investigators concluded, “[I]n this first large clinical study including 544 patients, whole-body MRI was able to discern over 30% of patients with [smoldering myeloma] presenting with patterns of tumor cell infiltration in the bone marrow similar to those of [multiple myeloma]. Given that many patients with [smoldering myeloma] develop symptomatic disease within 1 to 2 years, in the future, advanced imaging may play a major role in defining patients with [smoldering myeloma] who should be candidates for early treatment.”
Ligand-induced Stat3 Signaling Stronger at Relapse in Pediatric AML
Alexandra M. Stevens, MD, and colleagues from Baylor College of Medicine in Houston, assessed whether changes in STAT signaling pathways indicating strengthening of pathways involved in chemoresistance could be found at relapse in pediatric AML patients.10 Their group had previously shown that Stat3 signaling profiles are associated with outcome in pediatric AML; in particular, they found that patients with blasts sensitive to both granulocyte colony-stimulating factor (G-CSF, Neupogen) and interleukin (IL)-6, as measured by increased tyrosine phosphorylation of Stat3 (pY-Stat3), had significantly improved event-free and overall survival compared with patients with blasts resistant to one or both of the ligands.
In the current study, 21 paired diagnosis and relapse samples from pediatric patients were assessed after exposure to two different doses of G-CSF and IL-6. Significant increases in mean fluorescence intensity for pY-Stat3 were observed with both G-CSF doses, with increases occurring in 16 patients at each dose, and with both doses of IL-6, with increases occurring in 14 patients at the lower dose and in 12 patients at the higher dose. Parameters that did not change significantly between diagnosis and relapse included G-CSF receptor expression, gp130 expression, constitutive activity of pYStat3, and total Stat3 expression. A small but significant increase in phosphorylated 418-Src was observed.
The investigators concluded, “STAT pathway signaling patterns evolve between diagnosis and relapse in pediatric AML. Our data demonstrate that ligand-induced Stat3 signaling pathways evolve to become stronger at relapse. This suggests that the resistance seen to chemotherapy in relapsed patients may be in part due to the increased activity of this anti-apoptotic pathway in response to growth factors and cytokines present in the bone marrow niche. The increases in activity within the STAT pathway at relapse provide support for further development and evaluation of targeted agents against this pathway in relapsed patients with AML.”
Breast Cancer and Treatment-related AML after Taxane Therapy
Treatment-related AML is considered an independent marker of poor prognosis. The impact of treatment-related AML is not fully recognized, however, since it occurs years after completion of chemotherapy. Lindsey E. Roeker and colleagues from Mayo Medical School and the Mayo Clinic in Rochester, Minnesota, analyzed outcome of treatment-related AML in patients who had or had not received taxane therapy for breast cancer.11
Of a total of 88 women with AML diagnosed at Mayo Clinic between 1990 and 2011 included in the analysis, 65 had de novo AML and 23 (26%) had previously received treatment for breast cancer, including 14 who received a taxane as part of initial treatment (group 1) and 9 with no history of taxane exposure (group 2). Cytogenetic analysis showed diploidy in 71%, complex karyotypes in 14%, and chromosome 11 abnormalities in 0% of de novo AML patients, 8%, 8%, and 38%, respectively of group 1 patients, and 50%, 0%, and 33%, respectively, of group 2 patients. Cytogenetic risk was good in 14%, intermediate in 57%, and poor in 29% of group 1 patients and in 17%, 83%, and 0%, respectively, of group 2 patients.
There was no significant difference in complete remission rates between group 1 and group 2 (79% vs 83%). Overall, treatment-related AML was associated with reduced overall survival (P = .04). Median overall survival was 584 days in patients with de novo AML, 375 days in group 1 patients (P = .47 compared with de novo AML patients), and 222 days in group 2 patients (P < .001). The difference in overall survival between group 1 and group 2 was not statistically significant (P = .12).
The investigators concluded, “In agreement with previous reports, we found that [treatment-related] AML is a poor prognostic factor overall. However, patients with a history of breast cancer who had been treated with taxanes as a part of their initial chemotherapy regimen demonstrated similar survival as patients with de novo AML. Treatment-related AML patients only did significantly worse than patients with de novo AML if they had never received taxanes as part of their breast cancer therapy.” ■
Disclosure: Dr. Tobias May (Abstract 1491) is employed by, owns equity and patents, and receives royalties in association with InSCREENeX GmbH. All other authors of the studies summarized reported no potential conflicts of interest.
1. Agarwal A, MacKenzie R, Braziel RM, et al: Functional RNAi screen identifies novel cytokine and growth factor receptors critical for leukemia cell growth. 2012 ASH Annual Meeting. Abstract 1308. Presented December 8, 2012.
2. Zhang K, Pham LV, Tamayo AT, et al: Reversing metabolic and epigenetic cellular alterations to overcome chemo-resistance in aggressive B cell lymphomas. 2012 ASH Annual Meeting. Abstract 1305. Presented December 8, 2012.
3. de Vries A, Zwaan CM, Jansen JH, et al: Molecular aberrations in 107 children with myelodysplastic syndrome (MDS). 2012 ASH Annual Meeting. Abstract 2802. Presented December 9, 2012.
4. Chapuy B, Monti S, Takeyama K, et al: A structural basis for p53-deficiency, deregulated cell cycle and unfavorable outcome in diffuse large B-cell lymphoma. 2012 ASH Annual Meeting. Abstract 1534. Presented December 8, 2012.
5. Wagner B, Rebmann V, May T, et al: AML bone marrow microenvironment impairs dendritic cell maturation and antigen presentation. 2012 ASH Annual Meeting. Abstract 1491. Presented December 8, 2012.
6. Pallasch CP, Ilya L, Soto YM, et al: Drug-induced cytokine release sensitizes protective tumor microenvironments to antibody-mediated therapy. 2012 ASH Annual Meeting. Abstract 1335. Presented December 8, 2012.
7. Brunner AM,Feng Y, Drapkin BJ, et al: Association of baseline body mass index (BMI) with overall survival among patients over age 60 with acute myeloid leukemia (AML). 2012 ASH Annual Meeting. Abstract 1484. Presented December 8, 2012.
8. Strati P, Kantarjian HM, Cortes JE, et al: Biological and clinical features of patients with acute myeloid leukemia bearing trisomy 21. 2012 ASH Annual Meeting. Abstract 1488. Presented December 8, 2012.
9. Hillengass J, Kilk K, Listl K, et al: Over 30% of smoldering myeloma patients have tumor cell bone marrow infiltration patterns similar to multiple myeloma: a large (n=544) clinical study using whole-body MRI. 2012 ASH Annual Meeting. Abstract 2911. Presented December 9, 2012.
10. Stevens AM, Ruiz MJ, Redell MS: Increased responsiveness to ligand stimulation of the STAT pathway at relapse in acute myelogenous leukemia. 2012 ASH Annual Meeting. Abstract 3544. Presented December 10, 2012.
11. Roeker LE, Wolanskyj A, Elliott M, et al. Treatment-related AML patients previously treated with taxanes for breast cancer have similar outcomes as de novo AML. 2012 ASH Annual Meeting. Abstract 3555. Presented December 10, 2012.