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Introduction: Myeloperoxidase (MPO) is considered a specific marker of myeloid/non‐monocytic lineage in the diagnosis of mixed phenotype acute leukemia (MPAL). However, the clinical significance of isolated dim MPO expression in otherwise typical B lymphoblastic leukemia (B‐ALL; referred to as B/myeloid MPALisoMPO) in adult patients is unknown. Methods: We compared flow cytometric immunophenotype and clinicopathological findings among cases of B/myeloid MPALisoMPO (n = 13), other MPAL subtypes (n = 10, B/myeloid and T/myeloid MPAL), B‐ALL (n = 64), and acute myeloid leukemia (AML, n = 58), using the 2016 WHO classification. For MPAL cases, MPO was reported as the percent of MPO positive blasts and its intensity (dim or moderate/strong). The pattern of heterogenous antigen expression (inversely coordinated expression between myeloid and lymphoid markers and cell size) was assessed. Results: Cases of B/myeloid MPALisoMPO showed a fairly homogenous single B‐lineage blast population with dim MPO expression whereas cases of other MPAL subtypes displayed heterogeneous antigen expression and moderate/strong MPO expression. The percent of MPO positive blasts in these two groups was similar. Expressions of CD15, CD117, and monocytic markers were more common in other MPAL than in B/myeloid MPALisoMPO. B/myeloid MPALisoMPO patients had similar overall and leukemia free survivals as B‐ALL patients and better than other MPAL patients. Conclusion: This is the first study to investigate the clinical significance of adult B/myeloid MPALisoMPO using the 2016 WHO classification. Our results suggest that B/myeloid MPALisoMPO clinically behaves more similarly to B‐ALL than to other MPAL subtypes, supporting the 2016 WHO classification to segregate this entity from other MPAL subtypes. [ABSTRACT FROM AUTHOR]

Objective: This paper describes the Precision Medicine Knowledge Base (PMKB; https://pmkb.weill.cornell.edu ), an interactive online application for collaborative editing, maintenance, and sharing of structured clinical-grade cancer mutation interpretations.Materials and Methods: PMKB was built using the Ruby on Rails Web application framework. Leveraging existing standards such as the Human Genome Variation Society variant description format, we implemented a data model that links variants to tumor-specific and tissue-specific interpretations. Key features of PMKB include support for all major variant types, standardized authentication, distinct user roles including high-level approvers, and detailed activity history. A REpresentational State Transfer (REST) application-programming interface (API) was implemented to query the PMKB programmatically.Results: At the time of writing, PMKB contains 457 variant descriptions with 281 clinical-grade interpretations. The EGFR, BRAF, KRAS, and KIT genes are associated with the largest numbers of interpretable variants. PMKB's interpretations have been used in over 1500 AmpliSeq tests and 750 whole-exome sequencing tests. The interpretations are accessed either directly via the Web interface or programmatically via the existing API.Discussion: An accurate and up-to-date knowledge base of genomic alterations of clinical significance is critical to the success of precision medicine programs. The open-access, programmatically accessible PMKB represents an important attempt at creating such a resource in the field of oncology.Conclusion: The PMKB was designed to help collect and maintain clinical-grade mutation interpretations and facilitate reporting for clinical cancer genomic testing. The PMKB was also designed to enable the creation of clinical cancer genomics automated reporting pipelines via an API. [ABSTRACT FROM AUTHOR]

Objectives: CD25 expression is associated with t(9;22)(q34;q11)/Philadelphia chromosome translocation (Ph);BCR-ABL1 rearrangement in B lymphoblastic leukemia/ lymphoma (B-LL). However, the significance of CD25 expression in Ph negative (Ph-) B-LL regarding residual disease (RD) and genetic abnormalities is largely unknown. Methods: CD25 expression by flow cytometry (FC) was correlated with Ph status in 95 newly diagnosed B-LL patients and with RD status in day 29 marrow measured by FC in the context of cytogenetic risk stratification in Ph- patients. Results: CD25 expression was greater in Ph positive (Ph+) patients (80%) than in Ph- patients (17%), predicting Ph+ with 80% sensitivity and 86% specificity. In Ph- patients, CD25 expression (in 14 patients, 16%) was associated with RD in the cytogenetic intermediate-risk group: detectable RD in 50% of CD25+ patients vs 14% of CD25- patients. Interestingly, one CD25+/Ph- patient had a Ph-like genotype (ZC3HAV1-ABL2 rearrangement), and another had dual MYC-IGH and BCL2-IGH rearrangements. Conclusions: Our findings not only confirm the predictive power of CD25 expression for Ph+ but also demonstrate that CD25 expression is associated with RD (a biomarker correlated with prognosis) in Ph- patients. The latter finding is likely associated with underlying molecular abnormalities, including Ph-like genotype. [ABSTRACT FROM AUTHOR]

Molecular investigations have led to increased therapeutic options for prostatic adenocarcinoma. A single case report of a PRPSAP1::NTRK3 gene fusion occurring in prostate cancer was previously reported. A review of the literature revealed that NTRK gene rearrangements are exceedingly rare molecular events in prostate cancer. NTRK gene fusions can be oncogenic drivers or develop as resistance mechanisms. The tumor-agnostic approvals of TRK inhibitors by the FDA provide additional rationale for molecular investigations of aggressive prostatic adenocarcinomas. This may prove to be an additional therapeutic option for patients with aggressive prostatic carcinomas refractory to initial therapy. We report a case of an aggressive castrate-resistant prostatic adenocarcinoma with a BMP6::NTRK3 gene fusion. [ABSTRACT FROM AUTHOR]

Introduction: Myeloperoxidase (MPO) is considered a specific marker of myeloid/non-monocytic lineage in the diagnosis of mixed phenotype acute leukemia (MPAL). However, the clinical significance of isolated dim MPO expression in otherwise typical B lymphoblastic leukemia (B-ALL; referred to as B/myeloid MPAL isoMPO ) in adult patients is unknown., Methods: We compared flow cytometric immunophenotype and clinicopathological findings among cases of B/myeloid MPAL isoMPO (n = 13), other MPAL subtypes (n = 10, B/myeloid and T/myeloid MPAL), B-ALL (n = 64), and acute myeloid leukemia (AML, n = 58), using the 2016 WHO classification. For MPAL cases, MPO was reported as the percent of MPO positive blasts and its intensity (dim or moderate/strong). The pattern of heterogenous antigen expression (inversely coordinated expression between myeloid and lymphoid markers and cell size) was assessed., Results: Cases of B/myeloid MPAL isoMPO showed a fairly homogenous single B-lineage blast population with dim MPO expression whereas cases of other MPAL subtypes displayed heterogeneous antigen expression and moderate/strong MPO expression. The percent of MPO positive blasts in these two groups was similar. Expressions of CD15, CD117, and monocytic markers were more common in other MPAL than in B/myeloid MPAL isoMPO . B/myeloid MPAL isoMPO patients had similar overall and leukemia free survivals as B-ALL patients and better than other MPAL patients., Conclusion: This is the first study to investigate the clinical significance of adult B/myeloid MPAL isoMPO using the 2016 WHO classification. Our results suggest that B/myeloid MPAL isoMPO clinically behaves more similarly to B-ALL than to other MPAL subtypes, supporting the 2016 WHO classification to segregate this entity from other MPAL subtypes., (© 2022 John Wiley & Sons Ltd.)

Objectives: The purpose of the present research was to determine the role of family functioning and psychological problems of drug addicts and non addicts by assessing the difference between the two groups. After detailed literature review it was hypothesized that scores on the variable of communication, affective expression and control among family members of addicts will be higher than non addicts. Furthermore scores on the variables of anger control problems, emotional distress and positive self will also be higher of addicts., Methods: This was a cohort study. A cluster sampling method was used. Sample of present research consisted of 240 adolescents divided into two groups of 120 addicts and 120 non-addicts each from different socio-economic status. General scale of Family Assessment Measure-Version III (FAM-III) was administered in order to measure the level of communication, value and norms whereas dyadic Relationship Scale was used to measure affective expression and control among the family members of addicts and non addicts. Renold Adolescent Adjustment Screening Inventory was administered in order to assess anger control problems, emotional distress and positive self in addicts and non addicts. t-test was calculated in order to determine the difference in the level of communication, value and norms, affective expression and control among families of addicts and non addicts. Furthermore difference in anger control problems, emotional distress and positive self between the addicts and non addicts was also determined by calculating t-test., Results: Results showed significant differences in the variables among the family members and there is also a significant difference between addicts and non addicts., Conclusion: Avenues for further research have been suggested.