Medical Specialties Commons^™

Caring For Young Adults With Cancer: A Systematic Review, Sarah M. Pelletier

All Graduate Theses, Dissertations, and Other Capstone Projects

Young adulthood is unique period of life in which critical developmental milestones are achieved amid dynamic physical, emotional, and social changes. During this period of life, young adults are charged with establishing personal and social independence. When challenged with a cancer diagnosis, the already turbulent late teens, twenties, and thirties are dramatically and permanently altered. Hence, the needs of young adults vary from that of their pediatric and older adult counterparts. The aim of this systematic review of the literature was to identify what age-specific needs must be addressed by healthcare professionals to enhance quality of care and outcomes for …

The Role Of Bca2 In Regulation Of Warburg-Like Glucose And Lactate Metabolism In Breast Cancer Cell Lines, Richard T. Arkwright Iii

Wayne State University Dissertations

Modified metabolism is a hallmark of cancer cell biology known as “The Warburg Effect,” characterized by increased glucose-consumption and lactate-production, providing the metabolites and energy necessary for rapid proliferation. Breast-cancer-associated-gene-2 (BCA2) is an E3-Ub-ligase known to modulate AMPK, the “master-regulator of energy-homeostasis.” BCA2 is an oncogene associated with poor patient-survival and breast cancer invasiveness. Phospho-proteomic analysis of siBCA2-MDA-MB-231 knockdown-(KD) revealed enrichment of Nicotinamide-Nucleotide-Adenylyl-transferase-1 (NMNAT1), an essential enzyme in nuclear NAD-synthesis and a tumor-suppressor.

Initial experiments demonstrated that glucose concentration was positively correlated with BCA2 and inversely with NMNAT1 protein expression. shBCA2-KD in MDA-MB-468/-231 reproduced the inverse correlation between BCA2 and …

Mucosa-Associated Microbiota In Barrett’S Esophagus, Dysplasia, And Esophageal Adenocarcinoma Differ Similarly Compared With Healthy Controls, Shajan Peter, Amanda Pendergraft,, William Vanderpol, Mel Wilcox, Kondal R. Kyanam Kabir Baig, Casey Morrow, Jacques Izard, Peter J. Mannon

Department of Food Science and Technology: Faculty Publications

Introduction: Alterations in the composition of the human gut microbiome and its metabolites have been linked to gut epithelial neoplasia. We hypothesized that differences in mucosa-adherent Barrett’s microbiota could link to risk factors, providing risk of progression to neoplasia.

Methods: Paired biopsies from both diseased and nonaffected esophagus (as well as gastric cardia and gastric juice for comparison) from patients with intestinal metaplasia (n = 10), low grade dysplasia (n = 10), high grade dysplasia (n = 10), esophageal adenocarcinoma (n = 12), and controls (n = 10) were processed for mucosa-associated bacteria …

Targeting Homologous Recombination Addicted Tumors: Challenges And Opportunities, Talia Golan, Jonathan Brody, Md

Kimmel Cancer Center Faculty Papers

Recent advances in next generation sequencing (NGS) and molecular subtyping of tumors have opened the door to clinically available targeted therapies. Although the treatment of many solid tumors still rely on a steady regimen of non-targeted chemotherapeutic agents, it is becoming increasingly more apparent that certain tumors with defects in DNA damage repair (DDR) genes may be exquisitely sensitive to DNA damaging agents or therapies targeting key elements of this pathway such PARP1, ATR, or ATM. Still, for tumors with DDR defects the challenges are multi-fold including: (I) identifying these tumors in patients in time for a window of opportunity …

The Effect Of A Sun Damage Simulation Photography App On The Skin-Protective Behavior Intentions Of Women With Children Age 18 Or Younger, James Bowlds

DNP Projects

Abstract

Background: Skin cancer is the most common form of cancer diagnosed in the U.S. annually, despite being a largely preventable disease through the limitation of ultraviolet radiation exposure. Attempts to decrease its incidence have focused on appearance-based interventions. These have been effective at improving sun-protective behaviors among various subpopulations including people of color. Anecdotal observations suggest mothers more frequently utilize sun protection for their children than on themselves.

Purpose: The purpose of this project was to gain an understanding of the sun protection practices and beliefs of Caucasian and African American mothers, to assess the response to an appearance-based …

A Quality Improvement Initiative To Reduce Time To Antibiotics In Oncologic Neutropenic Fever, Jordan Villars, Adam Binder

Phase 1

Introduction: This paper documents a Quality Improvement (QI) initiative using Plan-Do-Study-Act (PDSA) cycles to decrease time to antibiotics (TTA) in oncologic neutropenic fever (NF) patients in a large tertiary-care academic medical center to the national guideline target of 60 minutes.

Methods: We measured baseline NF TTA across hospital units in the summer of 2018 and analyzed factors underlying delays in antibiotic treatment. We then developed a multi-disciplinary team to implement four proposed interventions:

1. Ensure that oncology floors are appropriately stocked with antibiotics required for initial NF treatment
2. Implement a nursing based order set for treatment of new NF cases. …

Hepatocellular Carcinoma Treated With Microwave Ablation Prior To Liver Transplantation, Nicole Wagner, Amanda Smolock, Michael Markovitz, Varun Danda, Christopher Neely, Warren Maley, Jesse Civan, Colette Shaw

Phase 1

Introduction: Ablation is a minimally invasive procedure that limits local liver tumor progression and prolongs patients’ transplantation eligibility. Microwave ablation (MWA) utilizes higher temperatures than the standard of care, radiofrequency ablation (RFA), which increases efficiency. Meta-analyses compared MWA with RFA for the treatment of HCC and showed similar efficacy and safety between these modalities. However, limited pathologic data exists determining whether explanted tumors remained viable after MWA.

Methods: Our database was reviewed retrospectively for patients with HCC who underwent MWA prior to liver transplantation between 2013 and 2019. Patient demographics, etiology of disease, tumor size, procedure details, bilirubin, MELD, …

Determining The Role Of Surgery In Diagnosis And Treatment Of Primary Cns Lymphoma, Tyler Fox, Michael Baldassari, Lohit Velagapudi, Karim Hafazalla, Christopher J. Farrell, Md, James J. Evans, Md, David W. Andrews, Md, Kevin Judy, Md, Donald Ye, Md

Phase 1

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare entity typically treated with a combination of chemotherapy and radiation. The role of surgery is controversial, and biopsy may be non-definitive or injurious. We review our series of stereotactic and excisional biopsy as well as surgical debulking of PCNSL to quantify overall risk and benefits.

Methods: Patients with biopsy-confirmed intracranial PCNSL were identified from a large singlecenter academic institution between 2012-2018. Preoperative factors and perioperative outcomes were retrospectively reviewed.

Results: A total of 61 cases of PCNSL were identified. Most patients presented with confusion (23.0%), weakness/paralysis (19.7%), and gait disturbance …

Classify Multicategory Outcome In Patients With Lung Adenocarcinoma Using Clinical, Transcriptomic And Clinico-Transcriptomic Data: Machine Learning Versus Multinomial Models, Fei Deng, Lanlan Shen, He Wang, Lanjing Zhang

Children’s Nutrition Research Center Staff Publications

Classification of multicategory survival-outcome is important for precision oncology. Machine learning (ML) algorithms have been used to accurately classify multi-category survival-outcome of some cancer-types, but not yet that of lung adenocarcinoma. Therefore, we compared the performances of 3 ML models (random forests, support vector machine [SVM], multilayer perceptron) and multinomial logistic regression (Mlogit) models for classifying 4-category survival-outcome of lung adenocarcinoma using the TCGA. Mlogit model overall performed similar to SVM and multilayer perceptron models (micro-average area under curve=0.82), while random forests model was inferior. Surprisingly, transcriptomic data alone and clinico-transcriptomic data appeared sufficient to accurately classify the 4-category survival-outcome …

Treating Hematologic Malignancies During A Pandemic: Utilizing Telehealth And Digital Technology To Optimize Care., Adam F Binder, Nathan R Handley, Lindsay Wilde, Neil Palmisiano, Ana Maria Lopez

Department of Medical Oncology Faculty Papers

In late January 2020, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) was reported as an outbreak in Wuhan, China. Within 2 months it became a global pandemic. Patients with cancer are at highest risk for both contracting and suffering complications of its resultant disease, Coronavirus 19 (COVID-19). Healthcare systems across the world had to adapt quickly to mitigate this risk, while continuing to provide potentially lifesaving treatment to patients. Bringing care to the home through the use of telehealth, home based chemotherapy, and remote patient monitoring technologies can help minimize risk to the patient and healthcare workers without sacrificing quality …

Management Of Patients With Hematologic Malignancies During The Covid-19 Pandemic: Practical Considerations And Lessons To Be Learned, Alessandro Isidori, Laurence De Leval, Usama Gergis, Pellegrino Musto, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

The COVID-19 pandemic has created unprecedented hurdles to the delivery of care to patients with cancer. Patients with hematologic malignancies appear to have a greater risk of SARS-CoV-2 infection and severe disease due to myelosuppression and lymphopenia. The first challenge, therefore, is how to continue to deliver effective, curative therapy to vulnerable patients and at the same time avoid exposing them, and their health care teams (HCT), to SARS-CoV-2. An additional challenge is the timely completion of the diagnostic and staging studies required to formulate appropriate treatment plans. Deferred procedures and avoidance of multiple trips to the surgical, diagnostic, and …

The Impact Of Dietary Intake On Mortality Risk In Colorectal Cancer Survivors, Ellen Chow

Walden Dissertations and Doctoral Studies

The colorectal cancer (CRC) survivor population is increasing in the United States. The lack of effective dietary recommendations in recurrence prevention undermines the health-related quality of life of survivors. Grounded in the socioecological model, dietary behavior is a personal-level risk factor that individuals may control. This study investigated the CRC-specific mortality risk as predicted by diet quality, dietary fiber intake, and dietary fat intake in hope of contributing to future dietary recommendations. A secondary analysis using data from 1,166 CRC survivors in the Multiethnic Cohort Study was analyzed via Cox proportional hazard regression models to estimate mortality risk. Results from …

Pre-Clinical Models Of Small Cell Lung Cancer And The Validation Of Therapeutic Targets, Jane S.Y. Sui, Petra Martin, Steven G. Gray

Articles

Introduction: Small-cell lung cancer (SCLC) is an aggressive form of lung cancer that has a dismal prognosis. One of the factors hindering therapeutic developments for SCLC is that most SCLC is not surgically resected resulting in a paucity of material for analysis. To address this, significant efforts have been made by investigators to develop pre-clinical models of SCLC allowing for downstream target identification in this difficult to treat cancer.

Areas covered: In this review, we describe the current pre-clinical models that have been developed to interrogate SCLC, and outline the benefits and limitations associated with each. Using examples …

Targeting Epha2 In Hepatocellular Carcinoma: Uncovering Its Therapeutic Potential And Beyond, Hao Wang

Dissertations

Hepatocellular Carcinoma (HCC) remains one of the deadliest malignancies worldwide. One major obstacle to treatment is a lack of effective molecular-targeted therapies. Here, we identify EphA2 receptor tyrosine kinase as a clinically relevant target for HCC. EphA2 expression and signaling is enriched in human HCC and associates with poor prognosis. Loss of EphA2 suppressed the initiation and growth of HCC in vitro and in vivo. Furthermore, CRISPR/CAS9 mediated EphA2 inhibition significantly delayed tumor development in a genetically-engineered murine model of HCC. Mechanistically, we discovered that targeting EphA2 simultaneously suppresses both JAK1/STAT3 and AKT signaling, two separate oncogenic pathways in HCC. …

Tumor Immunology: Understanding The Immune System And Cancer To Enhance The Efficacy Of Cancer Immunotherapies, Natasha Malibu Lenart

Master's Theses

Tumor cells are notorious for their ability to escape immune surveillance, but developments in the understanding of the tumor microenvironment and how the immune system can be re-activated in tumors have had significant clinical impact. Commercially available and experimental methods such as adoptive cellular therapy, cytokine stimulation, and immune checkpoint blockade are promising immunotherapies for a variety of cancers, including solid tumors and hematological malignancies. However, induction of persistent, long-term anti-tumor immunity after initial treatment is infamously difficult. as a result, scientists are searching for new approaches to improve established immunotherapies. by employing combination treatments or enhancing the functionality of …

High Lymph Node Positive To Sampled Ratio As A Potential Indication For Postoperative Radiation Therapy In Patients With Pn2 Non-Small-Cell Lung Cancer, Nikhil P Mankuzhy, Muayad F Almahariq, Craig W Stevens, Thomas J Quinn

Articles

Background: The role for postoperative radiation therapy (PORT) for patients with non–small-cell lung cancer (NSCLC) with mediastinal lymph node (LN) involvement (pN2 disease) is controversial. We performed a SEER analysis comparing surgery alone with PORT among patients with pN2 NSCLC. As we await the final results of the LUNG ART trial, a subset of patients with a high LN positive to sampled (LPR) ratio may benefit from PORT. Patients/methods: Patients with pN2 NSCLC, ranging from 1989-2016, were assessed from the Surveillance, Epidemiology and End Results (SEER) database. A propensity score (PS)-matched, inverse probability of treatment weighting (IPTW) analysis was conducted …

Characterizing Glycosaminoglycan And Glycosaminoglycan-Oligo Interactions With Cancer Stem Cells And Their Regulators, Rahaman Navaz Gangji

Theses and Dissertations

Tumor metastasis and recurrence account for more than 90% of cancer-associated deaths and are thought to occur due to a small subpopulation of neoplastic cells known as cancer stem cells (CSCs). Because CSCs are resistant to conventional chemotherapy, there is a critical need to develop CSC-targeting agents. Microenvironmental components, especially glycosaminoglycans (GAGs), play a key role in regulating CSC phenotype. GAGs such as heparan sulfate (HS) interact with hundreds of proteins and influence a variety of biological processes including tumor proliferation, angiogenesis, metastasis and stem cell biology.

Recently, the Desai and Patel laboratories have demonstrated that a hexasaccharide form of …

The Effects Of Autophagy And Senescence On Sensitivity To Cisplatin In Head And Neck Cancer, Zara H. Siddiqui

Theses and Dissertations

While current treatments in cancer, such as chemotherapy and radiation, can generally be effective in eliminating disease in patients, there also exists the possibility of recurrence of cancer cells over time. In patients diagnosed with locally advanced head and neck carcinoma, about 50-60% develop a loco-regional recurrence within two years, and 20-30% of patients develop metastatic disease at distant sites in the body [5]. On a cellular level, one mechanism for this survival may be that natural mechanisms such as autophagy and senescence play a role in allowing cells to survive after undergoing treatment. One standard of care chemotherapy for …

New Persistent And Chronic Opioid Use In Cancer Survivors After Curative Intent Radiation, Elena V. Fernández

Theses and Dissertations

Background: Emerging evidence suggests that as more patients are surviving cancer, new persistent opioid use (no prior exposure to opioids before cancer therapy but requiring opioid prescriptions after curative intent treatment; NPOU) is of greater concern. In patients receiving curative intent radiation (definitive radiation therapy and as treatment for cure; CIR), the extent to which patients develop NPOU or continue opioid use (COU) following CIR is not known. Neither are factors associated with NPOU or COU, opioid doses, or time to discontinuation (TTD) of opioids in 5CS known. Objectives: Describe longitudinal trends opioid use in cancer survivors who received CIR, …

Lsd1 Promotes Bladder Cancer Progression By Upregulating Lef1 And Enhancing Emt., Qiubo Xie, Tang Tang, Jian Pang, Jing Xu, Xingxia Yang, Linang Wang, Yiqiang Huang, Zhuowei Huang, Gaolei Liu, Dali Tong, Yao Zhang, Luofu Wang, Dianzheng Zhang, Weihua Lan, Qiuli Liu, Jun Jiang

PCOM Scholarly Works

Epithelial-to-mesenchymal transition (EMT) is one of the important underlying molecular mechanisms for most types of cancers including bladder cancer. The precise underlying molecular mechanism in EMT-mediated bladder cancer progression is far from completed. LSD1, a histone lysine-specific demethylase, is known to promote cancer cell proliferation, metastasis, and chemoresistance. We found in this study that LSD1 is highly upregulated in bladder cancer specimens, especially those underwent chemotherapy, and the elevated levels of LSD1 are highly associated with bladder cancer grades, metastasis status, and prognosis. Inhibiting or knockdown LSD1 repressed not only EMT process but also cancer progression. Mechanistically, LSD1 complexes with …

Targeting The Tumor Core: Hypoxia-Responsive Nanoparticles For The Delivery Of Chemotherapy To Pancreatic Tumors, Matthew I. Confeld, Babak Mamnoon, Li Feng, Heather Jensen Smith, Priyanka Ray, James Froberg, Jiha Kim, Michael A. Hollingsworth, Mohiuddin Quadir, Yongki Choi, Sanku Mallik

Journal Articles: Eppley Institute

In pancreatic ductal adenocarcinoma (PDAC), early onset of hypoxia triggers remodeling of the extracellular matrix, epithelial-to-mesenchymal transition, increased cell survival, the formation of cancer stem cells, and drug resistance. Hypoxia in PDAC is also associated with the development of collagen-rich, fibrous extracellular stroma (desmoplasia), resulting in severely impaired drug penetration. To overcome these daunting challenges, we created polymer nanoparticles (polymersomes) that target and penetrate pancreatic tumors, reach the hypoxic niches, undergo rapid structural destabilization, and release the encapsulated drugs. In vitro studies indicated a high cellular uptake of the polymersomes and increased cytotoxicity of the drugs under hypoxia compared to …

The Longitudinal Parallel Process Analysis Of Biomarkers Of Oxidative Stress, Symptom Clusters, And Cognitive Function In Children With Leukemia, Mary C Hooke, Daniel Hatch, Marilyn J Hockenberry, Susan Whitman, Ida Moore, David Montgomery, Kari Marano, Pauline Mitby, Michael E Scheurer, Olga Taylor, Wei Pan

Faculty, Staff and Students Publications

Background: During treatment for acute lymphoblastic leukemia (ALL), children report co-occurring symptoms of fatigue, sleep disturbance, pain, nausea, and depression as a symptom cluster. Central nervous system–directed ALL therapies also put children at risk for cognitive impairments. Cancer therapies can cause an increase in oxidative stress, which may contribute to treatment-related symptoms. This study examined the longitudinal relationships between biomarkers of oxidative stress in the cerebrospinal fluid, the Childhood Cancer Symptom Cluster–Leukemia (CCSC-L), and cognition, in children over the first year of ALL treatment. Methods: Glutathione (GSH) biomarkers of oxidative stress were measured in cerebrospinal fluid collected during treatment lumbar …

Acute Lymphoblastic Leukemia Presenting Initially As Spinal Cord Compression: When Chemotherapy Alone Is Enough, Albert Jang, Kallie N Kram, Scott N Berger, Mahmoud R Gaballa, Lee B Lu, David R Dunaway, Courtney N Miller-Chism

Faculty, Staff and Students Publications

Spinal cord compression (SCC) is a rare initial presentation and complication of acute lymphoblastic leukemia (ALL) with nearly all reported cases occurring in the pediatric population. We report a 38-year-old previously healthy man who presented with acute on chronic lower back pain, gait instability, urinary retention, and severe thrombocytopenia. Radiologic examination revealed two soft tissue masses of the thoracic spine associated with compression fractures causing spinal canal narrowing and cord compression. Bone marrow biopsy confirmed the diagnosis of ALL. Immediate initiation of high-dose corticosteroids and systemic chemotherapy resolved the patient's symptoms without radiation therapy or surgical intervention. After two courses …

Association Between Obesity And Hormone Receptor Characteristics Of Primary Breast Cancer At Cipto Mangunkusumo General Hospital, Jakarta, In 2017, Hardian Gunardi, Diani Kartini

The New Ropanasuri Journal of Surgery

Introduction. Obesity is an independent risk factor and prognostic factor of primary breast cancer. Abundant adipose tissue would lead to increment of blood estrogen level; thus, promoting proliferation of cancer cell, especially those with positive estrogen receptor (ER) and progesterone receptor (PR). No study reported the association between obesity and hormone receptor characteristics of primary breast cancer in Indonesia.

Method. We collected cases of primary breast cancer which is diagnosed and undergone immunohistochemistry examination at Cipto Mangunkusumo General Hospital in 2017. The subjects divided into obese group and non-obese group. The ER and PR characteristics of both groups were compared …

Cholangiocarcinoma Presenting As Humoral Hypercalcemia Of Malignancy: A Case Report And Literature Review, Burak Erdinc, Preethi Ramachandran, Ruchi Yadav, Sonu Sahni, Gardith Joseph

Touro College of Osteopathic Medicine (New York) Publications and Research

Humoral hypercalcemia of malignancy (HHM) is most commonly encountered in squamous cell carcinoma (SCC) of different organs, and It is characterized by elevated parathyroid hormone-related peptide (PTHrP) levels. It may be seen as a manifestation of cholangiocarcinoma (CCC) at presentation and later in the course of the disease. However, HHM due to intrahepatic cholangiocarcinoma is a rare association and is associated with a poor prognosis. We herein report a case of hypercalcemia presenting as the first manifestation of an underlying rare variant of intrahepatic cholangiocarcinoma. Our patient is a 57-year-old male who presented to the emergency room with severe symptoms …

Chloroquine Induction Par-4 And Treatment Of Cancer, Vivek M. Rangnekar

Radiation Medicine Faculty Patents

Described herein are methods for treating cancer in a subject in need thereof by administering chloroquine, or a salt or prodrug thereof, optionally with another agent that promotes Par-4 production to induce prostate apoptosis response-4 (Par-4) production by host cells, particularly non-cancerous host cells, to promote apoptosis in cancer cells, including androgen insensitive prostate cancer cells.

Evaluation Of A Technology-Based Survivor Care Plan For Breast Cancer Survivors: Pre-Post Pilot Study., Talya Laufer, Bryan Lerner, Anett Petrich, Anna Quinn, Leah Ernst, Alicin Roop, Janet Knoblauch, Nick C. Leasure, Rebecca J. Jaslow, Sarah Hegarty, Amy Leader, Andrea Barsevick

Department of Medical Oncology Faculty Papers

BACKGROUND: As of 2016, almost 16 million individuals were cancer survivors, including over 3.5 million survivors of breast cancer. Because cancer survivors are living longer and have unique health care needs, the Institute of Medicine proposed a survivor care plan as a way to alleviate the many medical, emotional, and care coordination problems of survivors.

OBJECTIVE: This pilot study for breast cancer survivors was undertaken to: (1) examine self-reported changes in knowledge, confidence, and activation from before receipt to after receipt of a survivor care plan; and (2) describe survivor preferences for, and satisfaction with, a technology-based survivor care plan. …

Mta3 Represses Cancer Stemness By Targeting The Sox2ot/Sox2 Axis, Liang Du, Lu Wang, Jinfeng Gan, Zhimeng Yao, Wan Lin, Junkuo Li, Yi Guo, Yuping Chen, Fuyou Zhou, Sai-Ching Jim Yeung, Robert P Coppes, Dianzheng Zhang, Hao Zhang

PCOM Scholarly Works

Cancer cell stemness (CCS) plays critical roles in both malignancy maintenance and metastasis, yet the underlying molecular mechanisms are far from complete. Although the importance of SOX2 in cancer development and CCS are well recognized, the role of MTA3 in these processes is unknown. In this study, we used esophageal squamous cell carcinoma (ESCC) as a model system to demonstrate that MTA3 can repress both CCS and metastasis in vitro and in vivo. Mechanistically, by forming a repressive complex with GATA3, MTA3 downregulates SOX2OT, subsequently suppresses the SOX2OT/SOX2 axis, and ultimately represses CCS and metastasis. More importantly, MTA3

Children’S Cancer Pain In A World Of The Opioid Epidemic: Challenges And Opportunities, Michelle Fortier, Sun Yang, Michael T. Phan, Daniel Tomaszewski, Brooke N. Jenkins, Zeev N. Kain

Psychology Faculty Articles and Research

The opioid crisis in the United States has grown at an alarming rate. Children with cancer are at high risk for pain, and opioids are a first‐line treatment in this population. Accordingly, there is an urgent need to optimize pain management in children with cancer without contributing to the opioid crisis. This report details opportunities for this optimization, including clinical practice guidelines, comprehensive approaches to pain management, mobile health, and telemedicine. It is vital to balance appropriate use of analgesics with efforts to prevent misuse in order to reduce unnecessary suffering and minimize unintended harms.

Methods To Impair Hematologic Cancer Progenitor Cells And Compounds Related Thereto, Craig Jordan

Internal Medicine Faculty Patents

Primitive or progenitor hematologic cancer cells have been implicated in the early stages and development of leukemia and malignant lymphoproliferative disorders, including acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and chronic lymphoid leukemia (CLL). Interleukin-3 receptor alpha chain (IL-3Ra or CD123) is strongly expressed on progenitor hematologic cancer cells, but is virtually undetectable on normal bone marrow cells. The present invention provides methods of impairing progenitor hematologic cancer (e.g., leukemia and lymphomic) cells by selectively targeting cells expressing CD123. These methods are useful in the detection and treatment of leukemias and malignant lymphoproliferative disorders. Also provided are compounds useful …