Jonathan E. Kolitz
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View article: TP53-mutated AML and treatment outcomes in the era of hypomethylating agent/venetoclax therapy
TP53-mutated AML and treatment outcomes in the era of hypomethylating agent/venetoclax therapy Open
Background TP53 mutations, present in 5–15% of acute myeloid leukemia (AML) cases, confer poor prognosis and may involve 17p deletions, point mutations, or both. While induction therapy with a hypomethylating agent (HMA) and venetoclax is …
View article: Predictors of 90-day mortality in elderly and unfit AML patients treated with single-agent hypomethylating agents or in combination with venetoclax
Predictors of 90-day mortality in elderly and unfit AML patients treated with single-agent hypomethylating agents or in combination with venetoclax Open
Background: Hypomethylating agents (HMAs) alone or in combination with venetoclax (VEN) offer a lower-intensity and tolerable treatment option for older and unfit acute myeloid leukemia (AML) patients. However, despite improved response ra…
View article: Normal B Cells in MBL follow divergent maturation pathways that correlate with the IGHV mutation status of the pre-leukemic clone
Normal B Cells in MBL follow divergent maturation pathways that correlate with the IGHV mutation status of the pre-leukemic clone Open
CLL and its precursor, monoclonal B-cell lymphocytosis (MBL), are associated with immune deficits. In MBL, the higher percentages of normal B cells (NBC) provide a unique opportunity to study B-cell defects. We compared transcriptomes of N…
View article: 17p cytogenetic changes in TP53-mutated AML
17p cytogenetic changes in TP53-mutated AML Open
Background In acute myeloid leukemia (AML), chromosomal rearrangements and point mutations involving the tumor suppressor gene TP53 confer adverse outcomes. We conducted a comprehensive analysis of 17p rearrangements in patients with TP53-…
View article: Real-world experience with front-line metronomic low-dose weekly decitabine and venetoclax in elderly and/or frail patients with MDS or AML
Real-world experience with front-line metronomic low-dose weekly decitabine and venetoclax in elderly and/or frail patients with MDS or AML Open
Background: Hypomethylating agents (HMAs) with and without venetoclax (Ven) have improved outcomes in elderly and less fit patients with high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, standard dosing sc…
View article: Prognostic and Therapeutic Implications of <i>BRAF</i> Mutations in Acute Myeloid Leukemia
Prognostic and Therapeutic Implications of <i>BRAF</i> Mutations in Acute Myeloid Leukemia Open
Mutations in the RAS/MAPK signaling pathway are recurrent in acute myeloid leukemia (AML), primarily involving NRAS and KRAS . In contrast, mutations in the gene encoding an effector protein, BRAF, occur at relatively lower frequencies in …
View article: Multi-dimensional analysis of adult acute myeloid leukemia cross-continents reveals age-associated trends in mutational landscape and treatment outcomes (Acute Myeloid Leukemia Cooperative Group & Alliance for Clinical Trials in Oncology)
Multi-dimensional analysis of adult acute myeloid leukemia cross-continents reveals age-associated trends in mutational landscape and treatment outcomes (Acute Myeloid Leukemia Cooperative Group & Alliance for Clinical Trials in Oncology) Open
The outcome of patients with acute myeloid leukemia (AML) worsens with increasing age. Dichotomization into “younger” and “older” patients is clinically routine and often dictates treatment options. We aimed to delineate whether molecular …
View article: Conventional and non-conventional antigen-binding sites promote the development and function of chronic lymphocytic leukemia stereotyped subset #4 clones
Conventional and non-conventional antigen-binding sites promote the development and function of chronic lymphocytic leukemia stereotyped subset #4 clones Open
Immunoglobulins (IGs) made by chronic lymphocytic leukemia (CLL) B cells are unique in that they bind themselves (homo-dimerize). This interaction leads to signal transduction with functional consequences that depend on the affinity of hom…
View article: Expanding the Spectrum of CSF3R-Mutated Myeloid Neoplasm Beyond Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia: A Comprehensive Analysis of 13 Cases
Expanding the Spectrum of CSF3R-Mutated Myeloid Neoplasm Beyond Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia: A Comprehensive Analysis of 13 Cases Open
Background: Genetic alterations in CSF3R, typically associated with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML), rarely occur in other myeloid neoplasms. Methods: This study characterized the clinical, …
View article: Expanding the Spectrum of CSF3R Mutated Myeloid Neoplasm Beyond Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia: A Comprehensive Analysis of 13 Cases
Expanding the Spectrum of CSF3R Mutated Myeloid Neoplasm Beyond Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia: A Comprehensive Analysis of 13 Cases Open
Background: Genetic alterations of CSF3R, typically associated with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML), rarely occur in other myeloid neoplasms. Methods: This study characterized the clinical, …
View article: Cytarabine Pharmacogenomics and Outcomes Among Children and Young Adults With Acute Myeloid Leukemia
Cytarabine Pharmacogenomics and Outcomes Among Children and Young Adults With Acute Myeloid Leukemia Open
Importance Therapeutic responses in acute myeloid leukemia (AML) demonstrate considerable variability both across and within established risk stratifications and age groups. Moreover, significant racial disparities persist, with Black pati…
View article: Chronic lymphocytic leukemia often arises by a multiclonal selection process
Chronic lymphocytic leukemia often arises by a multiclonal selection process Open
Although chronic lymphocytic leukemia (CLL) is diagnosed by identifying a circulating B-cell clone that exceeds 5x106/μL, additional distinct clones (ADC) have been identified in various studies. Notably, the numbers of ADC documented in t…
View article: Alemtuzumab in frontline therapy of adult acute lymphoblastic leukemia: Results of Cancer and Leukemia Group B 10102 (Alliance), a phase 1/2 study
Alemtuzumab in frontline therapy of adult acute lymphoblastic leukemia: Results of Cancer and Leukemia Group B 10102 (Alliance), a phase 1/2 study Open
Background Acute lymphoblastic leukemia (ALL) in adults is aggressive, with long‐term outcomes impacted by treatment resistance and toxicity. CD52 is expressed in most cases of B‐ and T‐lineage ALL. Alemtuzumab, a humanized immunoglobulin …
View article: Prognostic, biological, and structural implications of FLT3-JMD point mutations in acute myeloid leukemia: an analysis of Alliance studies
Prognostic, biological, and structural implications of FLT3-JMD point mutations in acute myeloid leukemia: an analysis of Alliance studies Open
The FLT3 gene frequently undergoes mutations in acute myeloid leukemia (AML), with internal tandem duplications (ITD) and tyrosine kinase domain (TKD) point mutations (PMs) being most common. Recently, PMs and deletions in the FLT3 juxtame…
View article: Delivery of Foreign Antigen Selectively to Membrane IgD on CLL and Normal B Cells Leads to Superior T-Cell Activation: A Possible Approach to Restore/Enhance T-Cell Immunity and T-Cell Help
Delivery of Foreign Antigen Selectively to Membrane IgD on CLL and Normal B Cells Leads to Superior T-Cell Activation: A Possible Approach to Restore/Enhance T-Cell Immunity and T-Cell Help Open
TCR mediated T cell activation is less robust in patients with CLL than healthy controls (HC), contributing to an immune deficiency that impairs quality and longevity of life. In HCs, T cell activation begins with myeloid or B cells acquir…
View article: Gilteritinib Results in Higher Remission and Transplant Rates Than Midostaurin but Does Not Increase the Post-Induction Mutational MRD Negative Rate: Results of the Phase 2 Randomized Precog 0905 Study in Newly Diagnosed <i>FLT3</i> Mutated AML
Gilteritinib Results in Higher Remission and Transplant Rates Than Midostaurin but Does Not Increase the Post-Induction Mutational MRD Negative Rate: Results of the Phase 2 Randomized Precog 0905 Study in Newly Diagnosed <i>FLT3</i> Mutated AML Open
Background: The addition of midostaurin (M), an oral multi-kinase inhibitor, to intensive chemotherapy (IC) prolongs survival in newly diagnosed (ND) FLT3 mutated (m) AML. It is not known if there is a benefit to more potent and selective …
View article: <i>PTPN11</i>Mutation Clonal Hierarchy in Acute Myeloid Leukemia
<i>PTPN11</i>Mutation Clonal Hierarchy in Acute Myeloid Leukemia Open
Summary Mutations in protein tyrosine phosphatase non-receptor type 11 ( PTPN11 ) have been considered late acquired mutations in acute myeloid leukemia (AML) development. To interrogate the ontogeny of PTPN11 mutations, we utilized single…
View article: BCL2 Protein Progressively Declines during Robust CLL Clonal Expansion: Potential Impact on Venetoclax Clinical Efficacy and Insights on Mechanism
BCL2 Protein Progressively Declines during Robust CLL Clonal Expansion: Potential Impact on Venetoclax Clinical Efficacy and Insights on Mechanism Open
CLL B cells express elevated pro-survival BCL2, and its selective inhibitor, venetoclax, significantly reduces leukemic cell load, leading to clinical remission. Nonetheless, relapses occur. This study evaluates the hypothesis that progres…
View article: Evidence that chronic lymphocytic leukemia arises from a multiclonal selection process
Evidence that chronic lymphocytic leukemia arises from a multiclonal selection process Open
Although chronic lymphocytic leukemia (CLL) is diagnosed by identifying in a patient’s blood a B-cell clone that exceeds 5x10 6 /µL, additional clones have on occasion been identified. To characterize such clones in patients with CLL, we a…
View article: Characterization of Comparative Clinical Outcomes and Molecular Features of Black Patients with Acute Promyelocytic Leukemia (APL) Reveals Similar Survival and Distinct Genomic Profiles
Characterization of Comparative Clinical Outcomes and Molecular Features of Black Patients with Acute Promyelocytic Leukemia (APL) Reveals Similar Survival and Distinct Genomic Profiles Open
Introduction: Although APL, a subtype of acute myeloid leukemia (AML), is an aggressive disease, its treatment was revolutionized with combination all- trans retinoic acid (ATRA) and arsenic trioxide (ATO), making APL a highly curable mali…
View article: The Ancestry-Related Landscape of Long Non-Coding RNAs (LncRNAs) in Acute Myeloid Leukemia (AML) and Its Impact on Patient (Pt) Survival
The Ancestry-Related Landscape of Long Non-Coding RNAs (LncRNAs) in Acute Myeloid Leukemia (AML) and Its Impact on Patient (Pt) Survival Open
Background In addition to molecular genetic and cytogenetic findings, gene expression profiles provide independent prognostic information in AML. Aberrant expression of non-coding RNAs, including lncRNAs, further inform pt prognosis. Howev…
View article: Transcriptomic Analyses Indicate That Pre-Leukemic B Cells from People with Monoclonal B Lymphocytosis Are Surprisingly Much Less Active Than Normal B Cells from People with Monoclonal B Lymphocytosis and from Healthy Donors
Transcriptomic Analyses Indicate That Pre-Leukemic B Cells from People with Monoclonal B Lymphocytosis Are Surprisingly Much Less Active Than Normal B Cells from People with Monoclonal B Lymphocytosis and from Healthy Donors Open
Introduction. Chronic lymphocytic leukemia (CLL) follows a stepwise developmental process, beginning in a specific group of normal B lymphocytes that undergo clonal expansion. These clonal expansions, known as monoclonal B lymphocytosis (M…
View article: Characterization of the Intraclonal Complexity of Chronic Lymphocytic Leukemia B Cells: Potential Influences of B-Cell Receptor Crosstalk with Other Stimuli
Characterization of the Intraclonal Complexity of Chronic Lymphocytic Leukemia B Cells: Potential Influences of B-Cell Receptor Crosstalk with Other Stimuli Open
Chronic lymphocytic leukemia (CLL) clones contain subpopulations differing in time since the last cell division (“age”): recently born, proliferative (PF; CXCR4DimCD5Bright), intermediate (IF; CXCR4IntCD5Int), and resting (RF; CXCR4BrightC…
View article: Sex-associated differences in frequencies and prognostic impact of recurrent genetic alterations in adult acute myeloid leukemia (Alliance, AMLCG)
Sex-associated differences in frequencies and prognostic impact of recurrent genetic alterations in adult acute myeloid leukemia (Alliance, AMLCG) Open
Clinical outcome of patients with acute myeloid leukemia (AML) is associated with patient demographics and genetic features. Although the associations of acquired genetic alterations with patients’ sex have been recently analyzed, their im…