Significance Aberrant Of CD133 Expression and Their Clinical Impact in Acute Lymphoblastic Leukemia among Sudanese Patients in Khartoum State

Background: Acute lymphoblastic leukemia (ALL) is a malignant disease that arises from several genetic mutations in a single B- or T-lymphoid precursor, resulting in altered blast cell survival, proliferation, and maturation. Objectives: This current study was aimed to determine the significance of aberrant CD133 and 45 expressions in Sudanese Patients with Acute lymphoblastic Leukemia, and their clinical significance in Khartoum state. Materials and Methods: One hundred Sudanese participants were enrolled in this study as follows: 88 Patients diagnosed with ALL as a case and 12 healthy controls donors were randomly selected. 2.5-5 mL of EDTA blood/bone marrow for flowcytometry from each patient and controls subject. Results: Eighty-eight newly diagnosed Sudanese patients with acute lymphocytic leukemia (ALL) were involved in this study, their age average is (15.7) and their stander deviation (SD) is 17.4. The frequency of aberrant markers concerning control groups was significantly associated with all patients in CD 45 with a P value (0.0001), while there was no difference between cases and control in the frequency of CD 133 antigen, there was no significant difference between age groups in the expression of different aberrant antigens. The study was significantly more expressed CD133 in males than females. Also no significant difference in hematological parameters between patients with or without expression of Aberrant CD 45 and 133 markers, while we found significantly high TWBCs in T. cell leukemia. Conclusion: Aberrant myeloid antigens CD45 was significantly associated with childhood and adult ALL and may be considered as important prognostic factors, while CD 133 were not associated with ALL.

Aberrant immunophenotypic expressions in acute lymphoid leukemia: an observational analytical study

Background: This study aims to find out the expression of aberrant immunophenotypic markers in acute lymphoid leukemia (ALL) and to co-relate its expression with cytogenetic and molecular data.Methods: Retrospective cum prospective study was carried out in 75 patients of ALL who presented to Apollo Gleneagles hospitals, Kolkata from January 2014 and March 2019. Flow cytometry analysis was done using FC500 (Beckman coulter) All cases were classified according to latest WHO classification.Results: Out of 75 cases of ALL, 23 cases (30.67%) showed aberrant cross-lineage expression. Amongst the B-ALL cases, the most common aberrant antigen expressed were myeloid antigens 17 cases (77.27%). Aberrant T- antigens were noted in 4 cases (18.10%). Aberrant co-positivity of myeloid as well as T-antigens was seen in 1 case (4.54%). The most common aberrant myeloid antigen expressed was CD33 (77.7%) followed by CD13 (22.2%) and then CD15 (11.1%). Co-positivity of CD13 and CD33 was noted in 2 cases. CD2 and CD33 co-positivity was noted in 1 case. The most frequently expressed aberrant T-antigen was CD2 seen in 3 out of 5 cases (60%).Conclusions: In B-ALL, the most common aberration was myeloid antigen positivity followed by cross-lineage T-antigen expression. Aberrant CD33 expression was most frequently associated with t(9;22) followed by t(12;21). Aberrant CD15 was most frequently associated with t(4;11). No association with adverse hematological parameters or any significant increase in cytogenetic and molecular abnormality was noted in cases expressing aberrant antigen in comparison to cases not expressing aberrant antigens.

Myeloperoxidase Expression in B-Lymphoblastic Leukemia by Immunohistochemistry as a Diagnostic Confounder

Background B-lymphoblastic leukemia (BLL) is a B lineage neoplasm that expresses typical immature B cell markers, but may also express myeloid-associated antigens. Myeloperoxidase (MPO) is a heme-containing peroxidase, which has been used as the single most specific myeloid marker when assigning lineage to acute leukemia. MPO positivity by immunohistochemistry (IHC) in BLL has been historically described in a subset of patients; however, further detailed comparison of IHC to flow cytometry and IHC methodology is described herein. Design The University of Washington pathology database was searched for new or relapsed adult BLL from 2011–2019. Cases with blasts >30% of marrow cellularity by morphology were selected. MPO IHC was performed using the Dako, polyclonal antibody (rabbit) on a Ventana instrument with streptavidin-biotin (SB) detection method. MPO IHC SB positive cases were also stained using the same antibody and platform, but a different detection method, multimer-optiview (MO). MPO IHC was called positive when >10% of neoplastic blasts showed expression. MPO positive blast percentage, staining intensity and pattern were assessed. Intensity: 0=negative, 1=mild, 2=moderate, 3=bright/same level as myeloids. Cytoplasmic pattern: homogenous or granular. Concurrent flow cytometry results and cytogenetic and/or molecular studies were reviewed. Results 35 cases were identified. Positive MPO IHC expression was present in 7/35 cases by SB method, with the percentage of MPO positive blasts ranging from 20–90% (majority >70%), all ranged from 1 - 2+ intensity and most (5/7) were homogenous pattern. 4/5 MPO SB positive cases were negative by MO detection method. MPO evaluation by flow cytometry was negative in 3 of 3 cases and myeloid associated antigens were negative or low on a subset. 2/8 BLL, BCR-ABL1 cases were MPO IHC positive by SB. Conclusion MPO staining by IHC in BLL is present in 17% of cases, often present in the majority of blasts, and positive using the SB detection system. This aberrant staining can be negated in most cases with the MO detection system. MPO expression by flow cytometry in MPO IHC SB positive cases were negative (3/3) and were low to absent for other myeloid antigens. We agree with prior studies that MPO IHC using the SB method can be a confounder for lineage assignment in acute leukemia.

Mixed Phenotype Acute Leukemia that Evolved from Myelodysplastic Syndrome with Excess Blasts

Myelodysplastic syndrome (MDS) that evolves into acute leukemia with blasts of mixed phenotypes has rarely been reported and has no distinct diagnostic category. Herein, we describe a 79-year-old Korean female patient with MDS–excess blasts (MDS-EB) that evolved into acute leukemia; the blasts simultaneously expressed B-lymphoid and myeloid antigens. The patient was diagnosed with MDS-EB with blasts of myeloid lineage coexpressing a few B-lymphoid antigens with 7q and 20q abnormalities. The disease progressed to acute leukemia with blasts carrying more B-lymphoid antigens, which was immunophenotypically compatible with B-lymphoid/myeloid acute leukemia. Unlike previously reported patients whose blast populations are bilineal, our patient is the first with biphenotypic acute leukemia that progressed from MDS. The diagnosis of our patient introduces the possibility that many other types of biphenotypic acute leukemia may have gone undiagnosed and encourages hematologists to designate a specific diagnostic category for this type of disease, so that it can more readily be detected and studied in the future.

THE IMMUNOPHENOTYPE OF ADULT T ACUTE LYMPHOBLASTIC LEUKEMIA IN MOROCCO

Background: There is paucity of detailed studies of adult T cell acute lymphoblastic leukemia (T-ALL) in developing countries reflecting the condition of these patients including clinical and biological features. Objective: This study was carried out to analyze the immunophenotypic characteristics of 40 Moroccan patients with T-ALL and its association with biological and clinical features. Patients and Methods: Between 2006 and 2009, 130 adult patients diagnosed with acute lymphoblastic leukemia (ALL) were immunophenotyped by 3-color flow cytometry using a panel of monoclonal antibodies. Cases presenting features of a T-lineage phenotype were subjected to detailed analysis including immunophenotypic, clinical and biological parameters. Results: Proportion of T-ALL among ALL Moroccan patients was 31.0%. Median age of patients was 28 years. Twenty-nine patients were females and 11 were males. 45.0% of patients (18/40) had features of immature T-ALL stages (pro-T and pre-T ALL), 30.0% (12/40) of CD1a+ cortical T-ALL stage and 25.0% (10/40) had a characteristic phenotype of medullary T-ALL. The frequencies of progenitor cell markers CD10, CD34 and TdT expression were 14.0; 57.5% and 50.0% respectively. The aberrant expression of B lineage associated antigen CD79a were positive in 20.5% of the cases and the aberrant expression of myeloid antigens CD13 and/ or CD33 was found in 22 (55.0%) cases. No significant association was encountered between TdT, CD34 or myeloid antigens positivity and high risk features at presentation as age, sex, and white blood cells. However, myeloid antigens (CD13 and/or CD33) was significantly associated with T-cell maturation stages (p = 0.009). Conclusion: To the best of our knowledge, this is the first report from North Africa of immunophenotypic study on adult T-ALL. Our findings indicate that the proportion of T-ALL among ALL in Morocco is similar to that reported in others Mediterranean countries like France and Italy and that myeloid-associated antigens expression is frequently associated with immature immunophenotype.

Expression of Myeloid Antigen in Neoplastic Plasma Cells Is Related to Adverse Prognosis in Patients with Multiple Myeloma

We evaluated the association between the expression of myeloid antigens on neoplastic plasma cells and patient prognosis. The expression status of CD13, CD19, CD20, CD33, CD38, CD56, and CD117 was analyzed on myeloma cells from 55 newly diagnosed patients, including 36 men (65%), of median age 61 years (range: 38–78). Analyzed clinical characteristics and laboratory parameters were as follows: serumβ2-microglobulin, lactate dehydrogenase, calcium, albumin, hemoglobin, serum creatinine concentrations, bone marrow histology, and cytogenetic findings. CD13+ and CD33+ were detected in 53% and 18%, respectively. Serum calcium (P=0.049) and LDH (P=0.018) concentrations were significantly higher and morphologic subtype of immature or plasmablastic was more frequent in CD33+ than in CD33− patients (P=0.022). CD33 and CD13 expression demonstrate a potential prognostic impact and were associated with lower overall survival (OS;P=0.001andP=0.025) in Kaplan-Meier analysis. Multivariate analysis showed that CD33 was independently prognostic of shorter progression free survival (PFS;P=0.037) and OS (P=0.001) with correction of clinical prognostic factors. This study showed that CD13 and CD33 expression associated with poor prognosis in patients with MM implicating the need of analysis of these markers in MM diagnosis.