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Philadelphia-like chromosome acute lymphoblastic leukemia (Ph-like ALL) is a new subtype of B-ALL that was discovered in 2009 and recognized in the 2016 revision of the World Health Organization criteria under the classification of myeloid neoplasms and acute leukemia. This new subtype has an extremely poor prognosis compared to that for other subtypes of ALL, with a 41% five-year overall survival (OS) rate. Ph-like ALL is chemoresistant, with a high minimum residual disease (MRD) level after induction therapy, and it is associated with a high relapse rate. Clinical trials are currently being conducted to study the effectiveness of specific tyrosine kinase inhibitors against different genetic alterations in Ph-like ALL patients and the effect of allogeneic hematopoietic cell transplants (allo-HCT) on treatments. This review summarizes the current findings on Ph-like ALL, focusing on its molecular landscape and clinical implications. [ABSTRACT FROM AUTHOR]

Purpose: Although the existing literature has explored the link between cognitive functioning and speech recognition in noise, the specific role of fluid intelligence still needs to be studied. Given the established association between working memory capacity (WMC) and fluid intelligence and the predictive power of WMC for speech recognition in noise, we aimed to elucidate the mediating role of fluid intelligence. Method: We used data from the n200 study, a longitudinal investigation into aging, hearing ability, and cognitive functioning. We analyzed two age-matched samples: participants with hearing aids and a group with normal hearing. WMC was assessed using the Reading Span task, and fluid intelligence was measured with Raven's Progressive Matrices. Speech recognition in noise was evaluated using Hagerman sentences presented to target 80% speech-reception thresholds in four-talker babble. Data were analyzed using mediation analysis to examine fluid intelligence as a mediator between WMC and speech recognition in noise. Results: We found a partial mediating effect of fluid intelligence on the relationship between WMC and speech recognition in noise, and that hearing status did not moderate this effect. In other words, WMC and fluid intelligence were related, and fluid intelligence partially explained the influence of WMC on speech recognition in noise. Conclusions: This study shows the importance of fluid intelligence in speech recognition in noise, regardless of hearing status. Future research should use other advanced statistical techniques and explore various speech recognition tests and background maskers to deepen our understanding of the interplay between WMC and fluid intelligence in speech recognition. [ABSTRACT FROM AUTHOR]

BackgroundAcute myeloid leukemia (AML) is commonly characterized by several chromosomal abnormalities resulting in the formation of chimeric genes that play various roles in leukemogenesis. Translocations resulting in the ETV6-ABL1 fusion gene are rare in AML and other hematologic malignancies with only thirty-two previously reported cases in the literature, five of which were AML.FindingsHerein, we report the case of a 73-year-old male with acute myeloid leukemia arising from MDS, negative for PDGFRA and PDGFRB, positive for bone marrow eosinophilia, rash, and marked fluid retention, which improved dramatically with imatinib therapy. Conventional cytogenetics revealed a t(3;9)(p25;q34), t(5;18)(q13;p11.2), and additional material of unknown origin at 12p11.2 in 2 out of 10 metaphases analyzed. Interphase FISH studies showed evidence of ETV6 (12p13) and ABL1 (9q34) rearrangements in 41.3 % and 5.7 % of the cells respectively. FISH studies on previously G-banded metaphases showed colocalization of ABL1 and ETV6 signals to the short arm of chromosome 3 at 3p25 suggesting a possible ETV6-ABL1 fusion. Subtelomeric metaphase FISH studies also showed the presence of a subtelomere 3p signal on the long arm of the derivative 9, and no subtelomere 3p signal on the derivative chromosome 12.ConclusionsThese findings suggest a complex rearrangement involving an insertion of ETV6 into 3p25 followed by a reciprocal translocation involving 3p25 and 9q34, resulting in a possible ETV6-ABL1 fusion. This case highlights the importance of FISH to characterize complex rearrangements in myeloid malignancies, particularly those resulting in clinically significant chimeric genes.

The American Society of Addiction Medicine (ASAM) has published clinical practice guidelines (CPGs) since 2015. As ASAM's CPG work continues to develop, it maintains an organizational priority to establish rigorous standards for the trustworthy production of these important documents. In keeping with ASAM's mission to define and promote evidence-based best practices in addiction prevention, treatment, and recovery, ASAM has rigorously updated its CPG methodology to be in line with evolving international standards. The CPG Methodology and Oversight Subcommittee was formed to establish and publish a methodology for the development of ASAM CPGs and to develop an ASAM CPG strategic plan. This article provides a focused overview of the ASAM CPG methodology. [ABSTRACT FROM AUTHOR]

Abstract Background B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy in pediatric patients and the leading cause of cancer-related death in children and young adults. Translocations of 9p24 involving JAK2 (9p24) and gain-of-function mutations of JAK2 with subsequent activation of the JAK2 kinase have been described in several hematological malignancies including B-ALL. However, rearrangements involving JAK2 are rare in B-ALL as only few cases have been described in the literature. Findings Herein, we present a case of pediatric B-ALL whose conventional cytogenetics revealed an abnormal karyotype with a reciprocal translocation involving 9p24 (JAK2) and 12p11.2. Fluorescence in situ hybridization (FISH) studies using the RP11-927H16 Spectrum Green JAK2 probe on previously G-banded metaphases confirmed the involvement of JAK2 in this rearrangement. Further FISH studies on the same previously G-banded metaphases using the LSI MLL probe helped to characterize an insertion of MLL into 6q27 as an additional abnormality in this karyotype. FISH studies performed on interphase nuclei also revealed an abnormal clone with MLL rearrangements in 23.6% of the nuclei examined as well as an abnormal clonal population with a deletion of the 5'IGH@ region in 88.3% of the nuclei examined. Conclusions Rearrangements of 9p24 can result in constitutive activation of JAK2, and have been observed in B-ALL. Rearrangements of the MLL gene have also been described extensively in B-ALL. However, rearrangements of MLL with a partner at 6q27 and in conjunction with a translocation involving JAK2 have not been previously described. This case pinpoints the importance of FISH and conventional cytogenetics to characterize complex rearrangements in which JAK2 and MLL are involved. The therapeutic targeting of JAK2 and MLL in cases like this may be prognostically beneficial.

Abstract The t(8;14)(q24.1;q32), the cytogenetic hallmark of Burkitt’s lymphoma, is also found, but rarely, in cases of chronic lymphocytic leukemia (CLL). Such translocation typically results in a MYC-IGH@ fusion subsequently deregulating and overexpressing MYC on der 14q32. In CLL, atypical rearrangements resulting in its gain or loss, within or outside of IGH@ or MYC locus, have been reported, but their clinical significance remains uncertain. Herein, we report a 67 year-old male with complex cytogenetic findings of apparently balanced t(8;14) and unreported complex rearrangements of IGH@ and MYC loci. His clinical, morphological and immunophenotypic features were consistent with the diagnosis of CLL.Interphase FISH studies revealed deletions of 11q22.3 and 13q14.3, and an extra copy of IGH@, indicative of rearrangement. Karyotype analysis showed an apparently balanced t(8;14)(q24.1;q32). Sequential GPG-metaphase FISH studies revealed abnormal signal patterns: rearrangement of IGH break apart probe with the 5’-IGH@ on derivative 8q24.1 and the 3’-IGH@ retained on der 14q; absence of MYC break apart-specific signal on der 8q; and, the presence of unsplit 5’-MYC-3’ break apart probe signals on der 14q. The breakpoint on 8q24.1 was found to be at least 400 Kb upstream of 5’ of MYC. In addition, FISH studies revealed two abnormal clones; one with 13q14.3 deletion, and the other, with concurrent 11q deletion and atypical rearrangements. Chromosome microarray analysis (CMA) detected a 7.1 Mb deletion on 11q22.3-q23.3 including ATM, a finding consistent with FISH results. While no significant copy number gain or loss observed on chromosomes 8, 12 and 13, a 455 Kb microdeletion of uncertain clinical significance was detected on 14q32.33. Immunohistochemistry showed co-expression of CD19, CD5, and CD23, positive ZAP-70 expression and absence of MYC expression. Overall findings reveal an apparently balanced t(8;14) and atypical complex rearrangements involving 3’-IGH@ and a breakpoint at least 400 Kb upstream of MYC, resulting in the relocation of the intact 5’-MYC-3’ from der 8q, and apposition to 3’-IGH@ at der 14q. This case report provides unique and additional cytogenetic data that may be of clinical significance in such a rare finding in CLL. It also highlights the utility of conventional and sequential metaphase FISH in understanding complex chromosome anomalies and their association with other clinical findings in patients with CLL. To the best of our knowledge, this is the first CLL reported case with such an atypical rearrangement in a patient with a negative MYC expression.

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin Lymphoma comprising of greater than 30% of adult non-Hodgkin Lymphomas. DLBCL represents a diverse set of lymphomas, defined as diffuse proliferation of large B lymphoid cells. Numerous cytogenetic studies including karyotypes and fluorescent in situ hybridization (FISH), as well as morphological, biological, clinical, microarray and sequencing technologies have attempted to categorize DLBCL into morphological variants, molecular and immunophenotypic subgroups, as well as distinct disease entities. Despite such efforts, most lymphoma remains undistinguishable and falls into DLBCL, not otherwise specified (DLBCL-NOS). The advent of microarray-based studies (chromosome, RNA, gene expression, etc) has provided a plethora of high-resolution data that could potentially facilitate the finer classification of DLBCL. This review covers the microarray data currently published for DLBCL. We will focus on these types of data; 1) array based CGH; 2) classical CGH; and 3) gene expression profiling studies. The aims of this review were three-fold: (1) to catalog chromosome loci that are present in at least 20% or more of distinct DLBCL subtypes; a detailed list of gains and losses for different subtypes was generated in a table form to illustrate specific chromosome loci affected in selected subtypes; (2) to determine common and distinct copy number alterations among the different subtypes and based on this information, characteristic and similar chromosome loci for the different subtypes were depicted in two separate chromosome ideograms; and, (3) to list re-classified subtypes and those that remained indistinguishable after review of the microarray data. To the best of our knowledge, this is the first effort to compile and review available literatures on microarray analysis data and their practical utility in classifying DLBCL subtypes. Although conventional cytogenetic methods such as Karyotypes and FISH have played a major role in classification schemes of lymphomas, better classification models are clearly needed to further understanding the biology, disease outcome and therapeutic management of DLBCL. In summary, microarray data reviewed here can provide better subtype specific classifications models for DLBCL.

Abstract T-cell prolymphocytic leukemia (T-PLL) is a rare form of leukemia composed of mature T-cells that usually presents in older people with a median age of 65. Most cases of T-PLL will harbor chromosomal abnormalities involving 14q11.2 (TCR alpha/delta), 14q32 (TCL1) or Xq28 (MTCP-1), abnormalities of chromosome 8, 12p and deletions of the long arm of chromosomes 5, 6, 11 and 13. Cytogenetics, FISH, comparative genomic hybridization (CGH) , SNP arrays with high resolution analysis have provided more precisely frequent submicroscopic gene and genomic lesions as well as breakpoints involved in the pathogenesis of this disease. One of the cornerstones to diagnose T-PLL are cytogenetic analysis. Here we summarize the current cytogenetic findings and we also describe two distinct cases of T-PLL where cytogenetics, FISH , morphologic analysis and flow cytometry helped to diagnose them accurately.

Identifying therapy-related AML (t-AML) of newly diagnosed acute leukemias is of great interest. Development of t-AML can occur after cytotoxic chemotherapy and/or radiation. We report a case of t-AML with CBFB::MYH11 fusion in a patient with a distant history of treated stage IIIB nodular sclerosing Hodgkin's lymphoma. We present the clinical course of the patient and the methods used to detect and monitor the rearrangement. Core binding factor AML (CBF-AML) after exposure to treatment is considered to be a good prognostic marker. The identification of these favorable AML subtypes such as CBF-AML highlights the importance of identifying genetic alterations, especially with increasing incidences of t-AML due to changes in choice of treatment and prognosis. [ABSTRACT FROM AUTHOR]

Penile cancer, while relatively rare compared to other male malignancies, has seen an increased global incidence, with 36,068 new cases reported in 2020. This condition primarily affects regions with low human development indexes, notably India, China and Brazil. The mainstay of treatment is often partial or total penectomy, which has a profound impact on patients' emotional and social lives. Due to limited options for early diagnosis, non-surgical treatments, restricted healthcare funding and the negative consequences of mutilating surgeries, penile cancer is often considered a neglected disease. Penile cancer exhibits various histological types, but penile squamous cell carcinoma (SCC) is the most prevalent, accounting for 95% of cases worldwide. Multiple risk factors are associated with this condition, largely tied to lifestyle behaviors, such as promiscuous sexual behavior, zoophilia, poor hygiene, phototherapy, smoking and obesity. Human papillomavirus (HPV) infection is a significant etiological factor, particularly in squamous cell carcinomas. The prevalence of HPV in penile neoplasia varies widely, and its association with mortality remains uncertain. [ABSTRACT FROM AUTHOR]

B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common leukemias affecting the pediatric population. It represents ~25% of cancer diagnoses among children. Specific genetic changes predict the prognosis in B-ALL with recurrent genetic changes. Here we present a case report of a 20-year-old male with B-ALL. The patient presented with acute onset worsening upper extremity pain with pallor, weight loss, dizziness, fatigue, and abnormal complete blood count (CBC). Conventional cytogenetics showed a karyotype of 46,XY, add(9)(q13),i(9)(q10)[19]. DNA FISH analysis performed on the bone marrow showed hemizygous deletion of the 9p21(CDKN2A) in 15.5% of the nuclei examined. The presence of an isochromosome 9q [i(9)(q10) is a rare event in pediatric B-ALL. An isochromosome 9q occurs in 0.6% of the patients studied in the literature. The significance of this abnormality in pediatric B-ALL is not clear. Profiling cases like this to understand the molecular mechanisms of rare chromosomal abnormalities and rare mutations in children with B-ALL could help us to better treat them. [ABSTRACT FROM AUTHOR]

The ribosomal protein S14 (RPS14) gene located at 5q33 codes for a protein involved in ribosomal biogenesis. The RPS14 gene has a length of 5.9 kb of DNA comprising 5 exons and 4 introns. It is possible that RPS14 is involved in the formation of pre-RNA 18s, an intermediate RNA that serves for the formation of the 40S small subunit of the ribosome. RPS14 haploinsufficiency (HI) produces alterations in intermediate RNA levels (pre-RNA 30S/18SE/18S), which are found in del(5q) MDS. In addition, RPS14 haploinsufficiency results in the formation of the MDM2 (double minute mouse E3 ubiquitin ligase)-RP (ribosomal protein) complex that prevents the MDM2-p53 interaction, generating an accumulation of p53 levels. This accumulation produces cell cycle arrest, impaired DNA repair, senescence, and apoptosis. RPS14 haploinsufficiency has been seen in MDS. Altered expression levels of RPS14 have also been reported in glioma, colorectal cancer, hepatocellular carcinoma, breast cancer, renal cell carcinoma, and primary myelofibrosis. [ABSTRACT FROM AUTHOR]

B-cell acute lymphoblastic leukemia (B-ALL) can afflict both adult and pediatric patients and is characterized by a build-up of B lymphoblasts. Here we present a case of a 25-year-old male patient with a history of B-ALL. Ninety percent of the bone marrow revealed pancytopenia with sheets of B lymphoblasts consistent with the diagnosis of B-ALL for acute pre-B lymphoblastic leukemia. The immunophenotype also presented predominant immature precursor B lymphoid cells positive for CD19, CD10, CD34, CD58, CD38, CD9, and TdT. Chromosome analysis of the bone marrow showed a complex karyotype described as 45~47,XY,i(8)(q10),der(10)add(10)(p11.1)add(10)(q23),-20,+1~2mar[cp3]/46,XY[36]. While IGH rearrangements were cryptic cytogenetically, DNA FISH analysis showed evidence of the IGH (14q32.2) gene rearrangement in 96.5% of the nuclei examined. These results were described as nuc ish(IGHx2)(5'IGH sep 3'IGHx1)[187/200],(5'IGH,3'IGH)x1~4(5'IGH con 3'IGHx0~2) [6/200]. The remaining probes were normal. Further studies using the MYC/IGH DC, DF probe from Abbott showed a gain of IGH signal in 7.5% of the nuclei examined: nuc ish(MYCx2,IGHx3)[15/200]. Metaphase FISH also showed that what appeared to be an isochromosome 8q was a derivative chromosome 8 defined as add(8)(p11.2) that contained a green IGH signal. In light of these results the karyotype was characterized as 45~47,XY,add(8)(p11.2),der(10)add(10)(p11.1)add(10)(q23),-20,+1~2mar[cp3].ish add(8) (p11.2) IgH+. IgH abnormalities are rare in B-ALL and are usually associated with a poor prognosis. However, at the present time our patient presented no evidence of persistent or residual disease and a cytogenetic response to the present therapy. [ABSTRACT FROM AUTHOR]

We present a case study of a 73-year-old female with a history of pancytopenia. The bone marrow core biopsy was suggestive of a myelodysplastic syndrome, unspecified (MDS-U). Chromosomal analysis of the bone marrow revealed an abnormal karyotype including gain of chromosomes 1, 4, 6, 8, 9, 19, and 20 in addition to loss of chromosomes 11, 13, 15, 16, 17, and 22. Also, additional material of unknown origin was found on 3q, 5p, 9p, 11p, 13p, 14p, and 15p; there were two copies of 19p, a deletion of 8q, and numerous unidentified rings and markers were present. This was characterized as: 75~77,XXX,+1,der(1;6)(p10;p10),add(3)(q27),+4,add(5)(p15.1),+6,+8,del(8)(q24.1),+add(9)(p24),-11,add (11) (p13),-13,add(13)(p10),add(14)(p11.2),-15,add(15)(p11.2), -16,-17,+19,add(19)(p13.3)x2,+20,-22, +0~4r,+4~10mar[cp11]/46,XX[8]. The cytogenetic analysis correlates with the concurrent FISH study which was positive for additional signals of EVI1(3q26.2), TAS2R1 (5p15.31), EGR1 (5q31.2), RELN (7q22), TES (7q31) RUNX1T1 (8q21.3), ABL1 (9q34), KMT2A (11q23), PML (15q24.1), CBFB (16q22), RARA (17q21), PTPRT (20q12), MYBL2 (20q13.12), RUNX1 (21q22.12) and BCR (22q11.2). Hyperdiploid karyotypes within the context of complex structural abnormalities are rare events usually associated with a poor prognosis in MDS. [ABSTRACT FROM AUTHOR]

The Janus Kinase 2 gene (JAK2) provides instructions for generating a protein that promotes the division and growth, or what is referred to as the proliferation, of cells. This generated protein relays signals in cells in order to promote cell growth, as well as help manage the count of white blood cells, red blood cells, and platelets that are generated within the bone marrow. Mutations and rearrangements of JAK2 are found in 3.5% of B-acute lymphoblastic leukemia (B-ALL) cases and in 18.9% of Down syndrome B-ALL patients, and are associated with a Ph-like ALL and a poor prognosis. However, there have been great challenges in understanding their role in this pathogenesis. In this review, we will discuss the most recent literature and trends associated with JAK2 mutations in patients with B-ALL. [ABSTRACT FROM AUTHOR]

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B-cell acute lymphoblastic leukemia (B-ALL) is one of the prevalent pediatric leukemias, accounting for 26% of cancers diagnosed in children 0-14 years of age. We present a case report of an 11-year-old girl with B-ALL. The patient was in complete remission nine months after diagnosis but passed away a month later from chemotherapy-induced hepatic failure, renal failure, and febrile neutropenia. Conventional cytogenetics showed a karyotype of 46,XX,del(5)(q31q35),add(6)(q23),del(7)(q32q36),add(11)(q23),ider(21)(q10)add(21) (q22),inc[20]. DNA FISH analysis performed on the bone marrow showed variant rearrangement of CRLF2, as well as loss of ETV6 signals and gain of RUNX1 signals. The presence of CRLF2 rearrangements within the context of a complex karyotype is often associated with CRLF2 overexpression and poor prognosis. The heterogeneity of B-ALL and the variability in the outcomes of patients that lack characteristic genetic abnormalities highlight the importance of profiling unusual genetic cases such as this one and continuing research to understand the molecular mechanisms of rarer mutations. [ABSTRACT FROM AUTHOR]