Acute erythroid leukemia (AEL), a rare and diagnostically complex subtype of acute leukemia, has undergone significant evolution in its diagnostic criteria since its initial description in 1912 by Copelli. Proper classification requires the integration of clinical history and diagnostic studies, including peripheral blood and bone marrow morphology, flow cytometry, cytogenetic and molecular studies. The latter have significant clinical and prognostic implications. Here, we discuss a case of AEL with a TP53 mutation and highlight the importance of integration of multiple test modalities in the accurate diagnosis of AEL versus acute myeloid leukemia, myelodysplasia- related (AML-MR). Additionally, we provide an overview of AEL and compare diagnostic changes in the WHO-HAEM5 and ICC.

Acute lymphocytic leukemia (ALL) is a hematologic malignancy marked by clonal growth of lymphoid precursors within the bone marrow, resulting in disrupted hematopoiesis. Chromosomal abnormalities provide valuable information on the development of ALL and serve as a key indicator of patient outcomes and treatment strategies. Numerous genetic abnormalities can be seen in ALL. Here, we described a case of a 15-year-old patient with B-ALL confirmed through biopsy and immunophenotyping. Conventional cytogenetic and FISH analysis showed t(3;7) with the presence of t(9;22). Translocation t(3;7) is rarely observed and is associated with a worse/ poor prognosis. Hence, the identification of such translocations in patients with B-ALL can aid in patient stratification, personalized medicine, and risk assessment.

Acute promyelocytic leukemia (APL) is cytogenetically characterized by the t(15;17)(q22;q21) translocation generating the PML::RARA fusion gene. Accurate laboratory diagnosis is essential for disease confirmation and prognostic prediction. In our cytogenetics laboratory, conventional GTG-banded karyotyping and fluorescence in situ hybridization (FISH) are routinely performed for all APL-suspected cases received from the chemotherapy unit of The Gujarat Cancer and Research Institute, Ahmedabad, after bone marrow/IPT requisitions. To document the cytogenetic abnormalities detected in APL-suspected cases using karyotyping and FISH, and to analyze their association with overall patient survival outcomes. This retrospective study included 32 APL-suspected cases referred to our laboratory. Each case underwent conventional cytogenetic analysis and FISH for the PML::RARA fusion. Clinical outcomes (Normal/Recovered, Discharged/Stable, Expired) were obtained from hospital records solely for correlation. Statistical analysis using SPSS included cross-tabulation and chi-square testing to assess the association between FISH status and patient outcomes. FISH detected PML::RARA fusion in 78.1% of cases (25/32), while 21.9% (7/32) exhibited negative or variant fusion patterns. All successful karyotyping studies demonstrated t(15;17), with occasional additional abnormalities. FISH-positive patients showed significantly better recovery rates (60%) compared to none among FISH-negative/variant cases. The association between FISH status and outcome was statistically significant (χ² = 11.165, p = 0.004). Cytogenetic evaluation using karyotyping and FISH provides essential diagnostic and prognostic insight in APL-suspected cases. FISH positivity strongly correlates with favorable outcomes, underscoring its value in routine diagnostic workflows.

Chronic myeloid leukemia (CML) is typically characterized by the presence of the BCR-ABL1 fusion gene on chomosome 22 resulting from a t(9;22)(q34;q11.2) translocation. We report a case of a 59-year-old female with CML in the chronic phase, initially presenting with thrombocytosis and diagnosed with t(9;22) via conventional karyotyping and fluorescence in situ hybridization (FISH). Nine years and seven months after the initial diagnosis, despite treatment with standard imatinib mesylate therapy (400 mg daily), conventional cytogenetic analysis revealed the emergence of trisomy 8 and a pericentric inversion of chromosome 16 (inv(16) (p13q22)) in cells that already carried the t(9;22). Bone marrow aspiration and biopsy showed 80% blasts, predominantly expressing myeloid markers CD13, CD33, CD117, along with HLA-DR and CD34. Both FISH and conventional karyotyping confirmed the presence of trisomy 8, inversion of chromosome 16, and t(9;22). Additionally, reverse transcription-polymerase chain reaction (RT-PCR) confirmed the presence of the BCR-ABL fusion gene. The coexistence of these genetic abnormalities is often associated with an aggressive clinical course, rapid disease progression, and chemotherapy resistance. Following disease progression, the patient was treated with a combination of hydroxyurea (500 mg) and decitabine (50 mg), and her tyrosine kinase inhibitor (TKI) therapy was switched to bosutinib (400 mg). Despite these interventions, she developed pleural effusions and lung metastases and ultimately passed away approximately seven months after initiating the new treatment due to relapsed disease and infectious complications.

We report the case of a 50-year-old male with acute myeloid leukemia (AML). Chromosome analysis revealed an abnormal karyotype with a t(6;20)(q13;q11.2) and a complex rearrangement leading to an extra derivative chromosome 1 [der(1)(14q32->14p13::1p13->1q44] which was confirmed by metaphase FISH. FISH analysis confirmed an extra copy of 1q25 in 30.5% [61/200] of the nuclei examined. Rearrangements leading to an extra copy of 1q are common in AML, but translocations involving chromosomes 6 and 20 are rarely observed. Both were seen previously in this patient, suggesting persistence of this patient's neoplasm. Only six cases in the literature describe translocations between chromosomes 6 and 20. However, the breakpoints found in our patient [t(6;20)(q13;q11.2)] appear to be unique. Further studies need to be conducted to determine if this is a common/rare abnormality in AML. Also, there was a complex rearrangement involving chromosomes 1 and 14, which was characterized by metaphase FISH, which is still a powerful tool for detecting complex rearrangements in the clinical cytogenetics laboratory.

Acute myeloid leukemia (AML) is a blood cancer characterized by the overproduction of myeloid precursors within the bone marrow, resulting in disrupted hematopoiesis. Chromosomal abnormalities provide valuable insights into the development of AML and serve as key indicators of patient outcomes and treatment strategies. Numerous genetic abnormalities can be seen in AML. Here, we describe a case of a 34-year-old patient with AML-M5. Biopsy and immunophenotyping confirmed AML-M5, while conventional cytogenetic and fluorescence in situ hybridization (FISH) analysis revealed trisomy of chromosomes 7 and 12, and an isochromosome (i)(Xq10). Trisomies of such chromosomes and i(Xq10) in combination are rare and carry different prognostic significance. In this case, the patient died within three days of diagnosis, demonstrating a poor prognosis. Hence, identification of such numerical chromosomal abnormalities in AML-M5 can help in patient stratification, tailored medicine, and risk assessment.

Chromosome translocations involving the RUNX1 gene at 21q22 are recurring abnormalities in acute myeloid leukemia (AML). t(8;21)(q22;q22) is the most common translocation involving the RUNX1 gene, which is categorized as an independent type of acute leukemia in the WHO classification system. The translocation results in a frame fusion of RUNX1::RUNX1T1, which is considered to be the pathogenesis of neoplasm development. The present report describes an AML case displaying a t(8;21)(q22;q22)-like translocation by initial chromosome analysis, but subsequent FISH analysis did not show the fusion signals corresponding to the RUNX1::RUNX1T1 fusion gene. Reverse transcriptase polymerase chain reaction (RT-PCR) also failed to identify the formation of the RUNX1::RUNX1T1 fusion gene. Reassessment of chromosome analysis in light of the FISH and RT-PCR data yielded a t(8;21) (q23;q22) translocation.

A 75-year-old male presented with back pain, abdominal discomfort, and weight loss, and was subsequently found to have a pancreatic head mass. Biopsy confirmed diffuse large B-cell lymphoma (DLBCL), and the patient achieved radiographic remission with chemotherapy. However, fluorescence in situ hybridization (FISH) analysis unexpectedly revealed Philadelphia chromosome-positive (Ph+) cells in the bone marrow and peripheral blood, establishing concurrent chronic myeloid leukemia (CML). Despite targeted therapy for CML, at last follow-up, the patient still has detectable BCR::ABL1. This rare case highlights the diagnostic importance of comprehensive staging and cytogenetic testing, as well as the therapeutic challenge of managing synchronous lymphoid and myeloid neoplasms.

Acute myeloid leukemia (AML) is a heterogeneous disease, indicated by its many conceivable cytogenetic mutations. Hyperdiploidy is a rare abnormality in AML, more prevalent in children than adults, with few other distinguishing associations. Chromosome totals above 49 in AML are very rare (2%). AML with hyperdiploidy can first be categorized as low or high hyperdiploidy (HH) based on modal chromosome number. High hyperdiploidy is then subcategorized into adverse, structural, or numerical HH. Across all three subtypes of HH, gains of chromosomes 8, 13, and 21 are the most frequent. Although the general survival outcomes of HH AML have remained inconsistent across several different studies, prognosis often relies on the modal chromosome number of the patient, with higher numbers having significantly poorer overall survival rates (OS). Here, we present an 80-year-old male patient with AML showing an abnormal karyotype presenting 78 to 81 chromosomes.

The Nobel Assembly of the Karolinska Institute (Sweden) awarded the 2024 Nobel Prize in Physiology or Medicine to Dr. Victor Ambros (University of Massachusetts Chan Medical School, Worcester, United States) and Dr. Gary Ruvkun (Massachusetts General Hospital, Boston, United States). This award recognized their joint discoveries of microRNAs and a novel mechanism of post-transcriptional regulation of gene expression in the worm C. elegans. This revolutionary breakthrough demonstrated first that miRNAs provide a refined control of development in C. elegans targeting mRNAs from distinct genes in an orderly fashion. Subsequent discoveries of many more microRNAs in other organisms across a wide evolutionary tree showed that these molecules and the regulatory mechanism of gene expression that they regulate are conserved throughout evolution. With more studies, these advances also triggered a realization that microRNAs play important roles in various critical biological processes (e.g., cellular growth, differentiation, development, cellular physiology, etc.). Other surveys reported abnormalities in microRNAs connected to multiple human diseases which, in turn, generated research interest in potential treatments focused on faulty microRNAs and their evaluation as potential markers of disease. This Nobel Prize caps nearly three decades of unprecedented advances in RNA research that include similar awards. A 2006 Nobel Prize honored the discovery of RNA interference that was initially described in 1998. The 2023 Nobel Prize paid tribute to the first effective human mRNA vaccines. Both advances generated practical applications of high significance including medical uses in humans. For these reasons, there is hope that in due time it will also be the case with microRNAs given their biological potential and many relevant physiological functions that they control.