Neutrophil scattering data driven pre-microscopic flagging of acute leukemic cases

ABSTRACT Background: The hematology analyzer, Sysmex XN-1000, generates white blood cell count with varying scattering intensities during a complete blood count (CBC) analysis. Objectives: The objectives of the study were to study the predictive role of median and coefficient of variation of neutrophil scattering items in blood samples for differentiation of leukemic subjects. Methods: We evaluated six neutrophil scattering parameters: neutrophil side scatter mean intensity, neutrophil side fluorescence light (SFL) mean intensity, neutrophil forward scatter mean intensity, neutrophil side scatter area distribution width (NE-WX), neutrophil SFL area distribution width (NE-WY), and neutrophil forward scatter area distribution width (NE-WZ), measured in white blood cell differential scattergram generated by the hematology analyzer (Sysmex XN-1000) at an academic medical center. Results: We collected 433 blood samples from acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) cases and normal controls. AML group showed highly significant differences in the mean values compared with the control group. Out of six neutrophil scattering items, NE-WX, NE-WY, and NE-WZ showed high efficiency, with area under the curve (AUC) values of 0.764, 0.748, and 0.757, respectively, to differentiate AML from ALL cases and control groups. When comparing combined acute leukemia cases (AML plus ALL) with the control group, NE-WX, NE-WY, and NE-WZ generated highly significant AUC values (0.840, 0.884, and 0.801, respectively). Conclusion: The neutrophil scattering parameters generated during CBC analysis provide a new tool for the prediction of acute leukemia and its lineage.

Eosinophilia with PDGFRB gene rearrangement and isolated del 5q; an extremely rare presentation of myeloid neoplasm

Introduction: Myeloproliferative neoplasms with PDGFRA, PDGFRB and FGFR1 rearrangements are reported to be very rare entities. Myeloid neoplasms with PDGFRB rearrangement have prominent eosinophilia, neutrophilia or monocytosis and presence of t (5;12)(q31~q33;p12-13) or variant translocation. Case Report: We report a 55 years old female patient who presented with eosinophilia along with predominant eosinophil precursors on bone marrow and concomitant isolated del (5q) and PDGFRB gene rearrangement which is an infrequent and rare finding. Conclusion: isolated acquired deletion of the long arm of chromosome 5 (del 5q) also known as 5q- syndrome, is a distinct hematologic disorder reported to be primary myelodys plastic syndrome which is found in females of middle age and usually presents with macrocytic anemia, oval macrocytes, with white blood cell counts normal or reduced, platelet counts normal or elevated and bone marrow exhibitery throid hypoplasia with megakaryocytes showing hypolobated nuclei

A 3-way Rare Variant Ph Translocation t(7;9;22) in a patient with Chronic Myeloid Leukemia.

Chronic Myeloid Leukemia (CML) is associated with translocation between chromosome 9 & chromosome 22, t(9;22)(q34;q11.2) and with the formation of BCR-ABL fusion gene. In few newly diagnosed CML cases, complex cytogenetics variants of the Philadelphia (Ph) chromosome can be observed with the involvement of a third chromosome other than chromosome 9 & chromosome 22. Here in, we describe a 45 yrs old male, diagnosed as CML in Chronic phase with a complex translocation involving chromosomes 7, 9 & 22. Cytogenetics investigations for confirmation of CML revealed 46,XY, t(7;9;22)(q11.2;q34;q11.2) in 100% metaphases counted. Fluorescence in-situ hybridization (FISH) showed BCR-ABL fusion signals pattern in 100% nucleated cells analyzed. A review of the literature revealed that CML patients with this translocation tend to have an aggressive course and poor outcome. Additional 3-way chromosome translocations associated with CML are also reviewed.

Molecular epidemiology of β-thalassemia in Pakistan: Far reaching implications.

Background: β -Thalassaemia, an autosomal recessive hemoglobinopathy, is one of the commonest genetically transmitted disorders throughout the world. Collective measures including carrier identification, genetic counseling and prenatal diagnosis are required for preventing β-thalassemia. Aim: To achieve this objective, Identification of the spectrum of genetic mutations, especially for various ethnic backgrounds in Pakistan. Therefore, we designed a cross sectional prospective study to identify the frequency of various gene mutations in different ethnic groups of Pakistan. Materials and Methods: Over a 5-year period, DNA from 648 blood samples {including specimens of chorionic villus sampling (CVS)} were analyzed for the twelve most common β-thalassemia mutations found in the Pakistani population by a Multiplex amplification refractory mutation system (ARMS). Each sample was analyzed for the mutation as well as the normal gene, appropriate with negative and positive controls, and reagent blanks. Results: Out of 648 samples mutations were identified in 640 (98.75%) samples by multiplex ARMS. 8 common β-thalassemia mutations were identified in 8 different ethnic groups accounting for 93.9% of the β-thalasemia alleles. Conclusions: Based on the outcome of this study a cost effective proposal is formulated for detection of β-thalassemia mutations.