3%). T-cell ALL constituted 24% (351 cases) of ALL. Common subtypes of AML included AMLM2 (27%), AMLM5 (15%), AMLM0 (12%), AMLM1 (12%), APML (11%), and AML t(8;21) (9%). CMLBC was commonly of myeloid blast crisis subtype (40 cases).Conclusion: B-cell ALL was the commonest subtype in children and AML in adults. Overall incidence of AML in adults was low (53% only). CD13 was most sensitive and CD117 most specific for determining myeloid lineage. A minimal primary panel of nine antibodies consisting of three myeloid markers (CD13, CD33, and CD117), B-cell lymphoid marker (CD19), T-cell marker (CD7), with CD45, CD10, CD34, and HLADR could assign lineage to 92% of AL. Cytogenetics findings lead to a change in the diagnostic subtype of myeloid malignancy in 38 (1.5%) cases. q

A large-cohort study (619) of acute lymphoblastic leukemia (ALL) revealed an ETV6/RUNX1 (previously known as TEL/AML1) incidence of 18% in pediatric B-cell precussor ALL, indicating no geographical heterogeinity. Association of CD34-negative phenotype, peak incidence in the 3- to 7-year age group, and a comparatively low frequency of ETV6 homologue loss in ETV6/RUNX1-positive cases were distinct findings in this series. Additional genetic changes, such as ETV6 loss, extra RUNX1, ETV6/RUNX1 duplication, and MLL aberrations in the ETV6/RUNX1-positive group, supported the hypothesis of the ETV6/RUNX1 leukemogenic model that these secondary changes are necessary for leukemogenesis rather than progression of disease. This study disclosed RUNX1 alterations in the ETV6/RUNX1-negative group of BCP-ALL that encourages the investigation of RUNX1 at a large scale with longer follow-up, which will focus on the prognostic importance and the underlying biology of disease.

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BACKGROUND:We present a clinico-hematological profile and treatment outcome of Biphenotypic Acute Leukemia (BAL). AIM: Study incidence and subtypes of BAL, correlate with age, morphology, and cytogenetic findings and correlate the clinico-hematological data with the treatment response. St Jude's and the EGIL's criteria have been compared for their diagnostic and clinical relevance. MATERIAL AND METHODS: Diagnosis was based on WHO classification, including clinical details, morphology, cytochemistry, immunophenotyping, and molecular genetics. We included those cases, which fulfilled the European Group for the Immunological Characterization of Acute Leukemia's (EGIL's) scoring system criteria for the diagnosis of BAL, as per recommendation of the WHO classification. RESULTS: There were 32 patients diagnosed with BAL, based on EGIL's criteria. Incidence of BAL was 1.2%. B-Myeloid (14 cases) followed by T-Myeloid BAL (13 cases) were the commonest subtypes. Polymorphous population of blasts (16 cases) was commonly associated with T-Myeloid BAL (10 cases). BCR ABL fusion positivity was a common cytogenetic abnormality (seven cases). Fifteen patients received chemotherapy; eight achieved complete remission (CR) at the end of the induction period. CONCLUSIONS: Pediatric BAL and T-B lymphoid BAL have a better prognosis. A comprehensive panel of reagents is required, including cytoplasmic markers; to diagnose BAL. St Jude's criteria is a simple, easy, and cost-effective method to diagnose BAL. The outcome-related prognostic factors include age, HLA-DR, CD34 negativity, and subtype of BAL. BCR-ABL expression is an important prognostic factor, as these cases will be labeled as Chronic myeloid leukemia (CML) in blast crisis with biphenotypic expression and treated accordingly.

The purpose of this retrospective study, the largest series in our country, was to illustrate the spectrum of subtypes and the immunophenotypic features of cases referred as acute leukemia (AL). Morphological diagnosis was correlated with cytochemical stains, immunophenotyping, and molecular genetic studies including fluorescent in-situ hybridization (FISH) and polymerase chain reaction (PCR). Two thousand five hundred and eleven consecutive new referral cases of Acute Leukemia (AL) between January 1, 2003 and December 31, 2006 were evaluated based on WHO classification. It included 1464 cases (58.3%) of Acute Lymphoblastic Leukemia (ALL), 962 cases (38.3%) of Acute Myeloid Leukemia (AML), 45 cases (1.8%) of Chronic Myelogenous Leukemia in blast crisis (CMLBC), 37 cases (1.5%) of biphenotypic acute leukemia (BAL), 1 case of Triphenotypic AL and 2 cases of Acute Undifferentiated leukemia (AUL). Common subtypes of ALL were B-cell ALL (76%) which comprised of intermediate stage/CALLA positive (73%), early precursor/Pro BALL (3%). T-cell ALL constituted 24% (348 cases) of ALL. Common subtypes of AML included AMLM2 (27%), AMLM5 (15%), AMLM0 (12%), AMLM1 (12%), APML (11%), AML t(8;21) (9%). CMLBC included myeloid blast crisis (40 cases), lymphoid blast crisis (2 cases), and biphenotypic leukemia (3 cases). CD13 was most sensitive and CD117 most specific for determining myeloid lineage. An immunoprofile of CD34+, HLADR+, CD14+ and CD33− is unlikely to be APML. CD117 is not a sensitive marker for APML and shows negative to weak continuous expression on promyelocytes. CD19 was expressed in 45% of FAB AMLM2 with t(8;21)(q22;q22). At least five cases of hepatosplenic gamma delta T-cell lymphomas were misdiagnosed as T-ALL based on a minimal selective panel where blasts expressed surface CD3. These cases were correctly diagnosed at relapse. Overall incidence of AML in adults is low (53% only). T-ALL is common in adolescent males. We recommend at least ten antibodies mainly CD13, CD33, CD117, CD10, CD19, HLADR, CD7, CD5 (or CD2), CD45 and CD34 as a primary minimal panel for a case of AL. Tdt is invaluable in work-up of pediatric T-cell neoplasm, to differentiate T-ALL from hepatosplenic gamma delta T cell lymphoma. Only 8% cases required additional markers (including intracytoplasmic markers) in the secondary panel for a lineage assignment. cCD22 is more sensitive than cCD79a for B-cell lineage assignment. Drawbacks of this study included referral bias, no clinical correlation, and three color immunophenotyping with FSC/SSC gating. Our approach for immunophenotyping was semi directed, a primary minimal panel followed by additional antibodies, as and when required. Cytoplasmic lineage specific markers (used in additional panel) for a lineage assignment were required only in 8% cases (n=199). We used only 14–20 antibodies per case (mean = 16), a number much less then many other laboratories. WHO classification has made it mandatory to do FISH/PCR to diagnose various leukemias which otherwise could be diagnosed with reasonable accuracy based on morphology, cytochemistry and flow cytometry like CML, APML, AMLM4Eo etc. Significant number of our FAB AMLM2 and AMLM4E0 cases did not show associated translocations. Few patients were partially treated by referring physician (steroids, blood transfusion, heavy metals etc), a category not addressed in WHO classification. Cytogenetics made a major difference in therapeutic decision in 0.8% cases only. Though flow cytometry is extremely popular amongst hematopathology laboratories, cytogenetics is available at few selected centers in countries with limited resources.