International Journal of Hematology

International Journal of Hematology | Vol. 17, No. 4, April 2026 | pp. 25–32
DOI: 10.46882/2026/IJH/000194

Original Article

Title: Impact of systemic hydroxyurea on plasma soluble intercellular adhesion molecule-1 levels and macrovascular velocity tracking in adult sickle cell anemia variations

Names of Authors: S. T. Adeyemi¹, U. V. Okoye², W. X. Salami³

Authors’ Affiliations: ¹Department of Haematology and Blood Transfusion, Obafemi Awolowo University, Ile-Ife, Nigeria; ²Department of Medicine, University of Nigeria Teaching Hospital, Enugu, Nigeria; ³Department of Paediatrics, Ahmavu Bello University, Zaria, Nigeria

Abstract: Severe endothelial activation and cell-to-wall adherence drive microvascular blockades and chronic pulmonary hypertension in sickle cell anemia. This prospective cohort study evaluated the long-term impact of optimized hydroxyurea therapy on plasma soluble intercellular adhesion molecule-1 (sICAM-1) concentrations and tricuspid regurgitant jet velocity (TRJV) modifications in 50 adult patients with steady-state sickle cell anemia variants (HbSS). Hydroxyurea was administered at maximum tolerated doses (15 to 25 mg/kg/day) over 12 months. Plasma markers were quantified using an enzyme-linked immunosorbent assay, and tricuspid velocities were tracked via Doppler echocardiography. Baseline mean sICAM-1 levels fell significantly from 344.2 ± 42.0 ng/ml to 168.4 ± 22.0 ng/ml at month 12 (P < 0.001). Concurrently, the proportion of patients presenting with elevated velocity metrics (TRJV ≥ 2.5 m/s) fell from 34.0% to 12.0%, reflecting a reduction in pulmonary vascular resistance. Adhesion molecule suppression correlated positively with an increase in fetal hemoglobin from 5.2% to 16.4%. These findings confirm that hydroxyurea successfully dampens endothelial cell activation, providing an accessible pharmacological pathway for preventing progressive macrovascular remodeling in adult sickle cell variants.

Keywords: Sickle cell anemia, hydroxyurea, ICAM-1, endothelial activation, tricuspid regurgitant jet velocity

Manuscript Timeline: Received: January 10, 2026; Revised: February 18, 2026; Accepted: March 10, 2026; Published: April 14, 2026

International Journal of Hematology | Vol. 17, No. 3, March 2026 | pp. 17–24
DOI: 10.46882/2026/IJH/000193

Review Article

Title: Structural mechanics and targeted biochemical inhibition of the menin-KMT2A interaction loops in adult acute leukemias

Names of Authors: M. A. Bello¹, O. R. Eze²

Authors’ Affiliations: ¹Department of Haematology, Aminu Kano Teaching Hospital, Kano, Nigeria; ²Department of Pathology, University of Benin, Benin City, Nigeria

Abstract: Chromosomal translocations involving the lysine methyltransferase 2A (KMT2A) gene drive high-risk leukemic transformations, characterized by poor clinical outcomes and limited response to standard multi-agent induction. This comprehensive review examines the molecular structural mechanics of the oncogenic KMT2A-fusion protein complex, detailing its mandatory dependence on the small-molecule cofactor menin to sustain high transcription levels of homeobox (HOXA) and MEIS1 target genes. This continuous up-regulation effectively blocks hematopoietic differentiation, locking adult myeloblasts or lymphoblasts in proliferative loops. Evolving therapeutic models focus on blocking this binding site using highly selective, small-molecule menin inhibitors like revumenib (SNDX-5613) and ziftomenib. These inhibitors sit directly within the hydrophobic central pocket of menin, disrupting the KMT2A interaction, down-regulating HOXA machinery, and inducing rapid morphologic differentiation. However, secondary drug resistance point mutations within the menin binding pocket present ongoing challenges. This review details structural biomarkers, mutant variant tracking, and clinical combination schedules designed to optimize menin-inhibition and maximize survival outcomes in adult KMT2A-rearranged leukemias.

Keywords: Acute leukemia, KMT2A rearrangement, menin inhibitors, revumenib, molecular mechanics

Manuscript Timeline: Received: December 01, 2025; Revised: January 12, 2026; Accepted: February 04, 2026; Published: March 15, 2026

International Journal of Hematology | Vol. 17, No. 2, February 2026 | pp. 9–16
DOI: 10.46882/2026/IJH/000192

Original Article

Title: Prevalence and molecular profiles of PPM1D and TP53 somatic mutations in therapy-related acute lymphoblastic leukemia variants

Names of Authors: G. M. Babalola¹, I. N. Nwosu², K. S. Abubakar³

Authors’ Affiliations: ¹Department of Haematology and Blood Transfusion, Lagos University Teaching Hospital, Lagos, Nigeria; ²Department of Medicine, University of Nigeria, Nsukka, Nigeria; ³Department of Pathology, Bayero University, Kano, Nigeria

Abstract: Genotoxic stress from prior cytotoxic regimens selects for chemoresistant stem cell clones harboring specific mutations, expanding the risk of therapy-related lymphoid malignancies. This cross-sectional study investigated the mutational prevalence and clinical phenotypes of protein phosphatase Mn²⁺/Mg²⁺ dependent 1D (PPM1D) and tumor suppressor TP53 gene variations in 64 adult lymphoma survivors presenting with therapy-related acute lymphoblastic leukemia. Genomic DNA was isolated from bone marrow aspirates, followed by deep next-generation sequencing assays. PPM1D exon 6 mutations were detected in 14.1% (9 of 64) of the leukemic cohorts, while TP53 variations occurred in 10.9% (7 of 64). Overlapping mutations in both DNA-damage response genes were documented in 3.1% of cases. Clinical phenotype models revealed that sub-clones with PPM1D variants exhibited extreme survival advantages under alkylating agent exposure, correlating with complex karyotypes and primary resistance to standard induction regimens. Screening for these chemoresistant variants provides essential molecular tracking vectors, helping pathologists separate therapy-induced acute transitions from de novo lymphoid expansions.

Keywords: Clonal hematopoiesis, PPM1D mutation, TP53 mutation, therapy-related lymphoblastic leukemia, next-generation sequencing

Manuscript Timeline: Received: November 05, 2025; Revised: December 14, 2025; Accepted: January 10, 2026; Published: February 18, 2026

International Journal of Hematology | Vol. 17, No. 1, January 2026 | pp. 1–8
DOI: 10.46882/2026/IJH/000191

Original Article

Title: Serum erythroferrone kinetics and absolute iron utilization markers in adult beta-thalassemia intermedia cohorts

Names of Authors: A. I. Ibrahim¹, C. D. Balogun², E. O. Ojo³

Authors’ Affiliations: ¹Department of Haematology, Ahmadu Bello University, Zaria, Nigeria; ²Department of Medicine, University of Ilorin, Ilorin, Nigeria; ³Department of Chemical Pathology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria

Abstract: Severe ineffective erythropoiesis drives profound hyperferritinemia and systemic iron loading in non-transfusion-dependent thalassemias, mediated by erythroblast-derived signaling peptides. This prospective clinical study evaluated serum erythroferrone (ERFE) kinetics, circulating hepcidin levels, and soluble transferrin receptor values in 45 adult patients presenting with confirmed beta-thalassemia intermedia. Serum biomarker concentrations were quantified utilizing high-sensitivity enzyme-linked immunosorbent assays. Adult thalassemic individuals exhibited a five-fold increase in steady-state serum erythroferrone levels (mean 128.4 ± 24.5 pg/ml) compared to healthy controls (P < 0.001). This overproduction of erythroferrone correlated inversely with bioactive plasma hepcidin-25 levels (r = -0.58, P < 0.01), leading to unchecked intestinal iron absorption and toxic macrophage release despite significant tissue iron deposition (ferritin > 900 ng/ml). Soluble transferrin receptor indices reflected immense marrow erythroid expansion. Tracking erythroferrone kinetics provides an accurate, non-invasive indicator of ineffective erythroid drive and systemic iron loading risk, helping clinicians optimize the timing for initializing iron chelation or therapeutic modulation before severe parenchymal target-organ damage manifests.

Keywords: Beta-thalassemia intermedia, erythroferrone, hepcidin suppression, ineffective erythropoiesis, iron overload

Manuscript Timeline: Received: October 14, 2025; Revised: November 20, 2025; Accepted: December 08, 2025; Published: January 14, 2026

International Journal of Hematology | Vol. 16, No. 10, October 2025 | pp. 73–80
DOI: 10.46882/2025/IJH/000188

Original Article

Title: Evaluation of automated immature reticulocyte fraction and red blood cell fragmentation flags in separating iron deficiency from hemolytic uremic syndrome variations

Names of Authors: Q. S. Abubakar¹, U. T. Maina²

Authors’ Affiliations: ¹Department of Haematology, National Hospital, Abuja, Nigeria; ²Department of Pathology, Bayero University, Kano, Nigeria

Abstract: Severe microcytic anemia fragments can mimic schistocytes on automated counters, requiring robust laboratory separation parameters to prevent inappropriate therapeutic decisions. This prospective diagnostic study evaluated the performance of automated immature reticulocyte fractions (IRF) and fragmented red blood cell (FRC) flags for separating absolute iron deficiency anemia from microangiopathic hemolytic uremic syndrome variations. Evaluations were conducted on 125 adult patients presenting with thrombocytopenia and microcytosis, and diagnoses were validated via serum ferritin, complement gene panels, and manual visual blood film schistocyte counts. Hemolytic uremic syndrome variants were confirmed in 50 cases, while 75 presented with severe iron deficiency anemia. The mean immature reticulocyte fraction was significantly higher in the microangiopathic cohort compared to the iron-deficient group (0.34 ± 0.08 versus 0.12 ± 0.03, P < 0.001), reflecting an intense bone marrow response. Conversely, automated fragmentation flags were elevated in both groups. Receiver operating characteristic analysis established a combined IRF and FRC model that achieved a diagnostic sensitivity of 91.2% and a specificity of 88.4% for identifying true destructive processes. Utilizing automated reticulocyte maturity indices provides an efficient, low-cost asset for screening complex hemolytic environments.

Keywords: Immature reticulocyte fraction, fragmented red cells, iron deficiency anemia, schistocytes, cell counter indices

Manuscript Timeline: Received: July 20, 2025; Revised: August 25, 2025; Accepted: September 12, 2025; Published: October 14, 2025

International Journal of Hematology | Vol. 16, No. 12, December 2025 | pp. 89–96
DOI: 10.46882/2025/IJH/000190

Short Communication

Title: Evaluation of automated microcytic cell mathematical indices in predicting latent iron deficiency in volunteer multi-donation adolescent female blood donors

Names of Authors: B. C. Akpan¹, D. E. Usman²

Authors’ Affiliations: ¹Department of Haematology, University of Calabar, Calabar, Nigeria; ²Department of Clinical Pharmacology, Ahmadu Bello University, Zaria, Nigeria

Abstract: Frequent blood donations in childbearing adolescent cohorts deplete biological iron pools, often inducing latent iron deficiency before total hemoglobin screening tests fall below acceptable thresholds. This diagnostic study evaluated the predictive performance of the Mentzer index and the Green and King mathematical cell counter formulas for identifying latent iron depletion in 120 regular adolescent female blood donors presenting with normal total hemoglobin levels (≥ 12.5 g/dl). Calculated indices were cross-validated against biochemical serum ferritin reference parameters. Latent iron deficiency, defined by a serum ferritin below 20 ng/ml, was confirmed in 24.1% (29 of 120) of the donor cohort. The Green and King formula achieved an isolated sensitivity of 89.6% and a positive predictive value of 76.1% for predicting depleted iron reserves, significantly outperforming the Mentzer index model (P < 0.05). Utilizing automated cell counter mathematical formulas offers an efficient, low-cost screening protocol to detect latent iron-restricted erythropoiesis and preserve donor safety.

Keywords: Blood donors, latent iron deficiency, Mentzer index, Green and King formula, donor selection

Manuscript Timeline: Received: September 15, 2025; Revised: October 22, 2025; Accepted: November 10, 2025; Published: December 14, 2025