The department is engaged in active research with investigations ranging from a basic to molecular level in the field leukemia, bleeding disorders, platelet function disorders, hemoglobinopathies, thalassemia etc. The department awards PhD degrees to postgraduates in the field of Biochemistry, Genetics and Biotechnology. The research workers have made a significant contribution to the Department by introducing, standardizing and monitoring the various modern molecular tests. They have contributed in the establishment of tests such as Prenatal diagnosis of Hemophilia, Multimeric analysis of vWD, screening for Thrombophilic mutations,estimation of gpIIb/IIIa in Glanzmanns Thrombasthenia, alpha3.7 and 4.2 deletions in Thalassemia, immunophenotypic and molecular studies (RTPCR) for Cytogenetics in diagnosis and management of haematological malignancies such as bcr/abl for chronic myeloid leukemia. Most of these tests are either not available or done at only select centers across the country. The Department also employs competent and qualified research officers to carry forward the studies.
a) ACUTE LEUKEMIAS
The Leukemia research laboratory has been carrying out extensive characterization of acute and chronic leukemias / by
(1) Southern blot analysis, (2) RT-PCR is being carried out for qualitative analysis of various transcripts in acute leukemias. bcr-/abl and PML RAR alpha.
Biology of lymphoid neoplasia in India as compared to the West showed a high relative incidence to T Cell ALL, absence of early age peak, difference in immunoglobulin, T-cell receptor and SIL-SCL gene rearrangements. ALL-& BCR-ABL gene rearrangements and multidrug resistance genes were also studied. Bcl-2 gene was found in only 11% of follicular lymphoma versus 70% in the West. RT-PCR based methods or the detection of t:15/17 and t: 8/21 in AML M3 and M2 are also being performed.
b) CHRONIC LEUKEMIAS:
Presentation of Chronic myeloid leukemia (CML) is at younger age as compared with developed countries. Mutation studies for Imatinib resistance and trials for better outcome of chronic myeloid leukemia patients are ongoing. Stem cell transplantation is offered to younger patients with matched sibling donor. Molecular studies of RT-PCR and RQ-PCR for CML translocations are being carried out.
Different protocols are being evaluated for better immunophenotyping and molecular genetic profile of chronic lymphoid leukaemia (CLL) for better understanding of pathogenesis.
Thalassemia is a common hemoglobinopathy found in north India. Due to the interplay of Hb E, and polymorphism of various genes the presentation of thalassemias may vary.
Endocrinopathies in these children are being investigated. Hydoxyurea is used for alleviating the severity of disease in children with thalassemia intermedia and sickle cell anemia. It has been observed that the prevalence of HIV, hepatitis B and C is quite high. Interferon therapy is able to eliminate hepatitis C virus inspite of high serum ferritin levels. Currently NMR studies are being carried out to correlate endocrinopathies with iron deposits over various endocrine glands. Molecular studies for detection of a thalassemia, are being conducted to determine its impact in modifying the severity of Thalassemia.
d) APLASTIC ANEMIA:
Fanconi anemia is a subtype of aplastic anemia, genetic studies are being performed to evaluate this disorder. Management of aplastic anemia with stem cell transplantation, Inj ATG and cyclosporine or with Stanazol with and without cyclosporin are being performed as per the type of aplastic anemia.
Immune Thrombocytopenic Purpura
Role of platelet associated antibodies is being evaluated in pathogenesis of immune thrombocytopenic purpura in children and adults. Various therapeutic modalities such as subcutaneous anti D, and combination therapy is being evaluated in patients with refractory ITP.
Platelet function defects like isolated PF3 availability defect, Glanzman’s thrombasthenia, Bernard Soulier disease, von Willebrand disease have been identified. Characterization of vWD using vWFAg, Ristocetin CoF Assay and multimer analysis are in progress. Carrier detection and subtyping of vWD is being carried out using vWF1 and vWF2 linkage markers. Effect of soya been therapy in patients with isolated PF3 availability defect has been encouraging. Molecular studies in Glanzman's Thrombasthenia are underway. Flow cytometry and Western blot analysis for the detection of GpIIb/IIIa defect in Glanzman’s Thrombasthenia is being carried out
Hereditary protein defects (Protein C, S deficiency, ATIII, APC resistance) the pathogenetic factors underlying Indian DVT, young stroke patients and recurrent abortions are being evaluated.
Role of Lupus anticogulants in recurrent abortions has been evaluated. A test (inosithin neutralisation test) has been devised to quantitate the LAC. Comparative evaluation of LAC and anticardiolipin antibodies is being evaluated in patients of SLE.
Molecular studies for underlying factor V leiden defect are in progress.
Molecular studies for rare coagulation disorders like F XIII deficiency, FV deficiency are in progress. ELISA and Heparin induced platelet aggregation are being used to detect heparin induced thrombocytopenia. ELISA for detecting Antiphospholipid antibodies (ß2 Glycoprotein antibodies) is being carried out. ELISA for detecting high levels of homocysteine in blood is also being carried out.
g) HEMOPHILIA A and B:
The Dept. of Hematology is well versed in the use of mutation detection techniques of intron 22 and 1 inversions as well as linkage markers like Bcl I, Xba1(long), VNTR (int 13 + 22). It is being used for carrier detection and prenatal diagnosis of hemophilia A. Hemophilia B carrier detection is being done using linkage markers Hhna-1,Mnd 1, Sal-1 etc.
EXTERNAL QUALITY ASSURANCE CONTROL PROGRAMME:
The Department of Hematology is coordinating the Indian Society of Hematology and Transfusion Medicine-AIIMS External Quality Assurance Programme in hemogram. This programme has been initiated from January 2003. 575 Medical colleges and laboratories are participating in this program and we are encouraging more laboratories to participate in it. Moreover, the NABL has made Department of Hematology, AIIMS as the nodal laboratory for External Quality Assessment in Hematology. Thus ISHTM-AIIMS EQAP provides a NABL recognize external quality assessment to a laboratory interested in NABL accreditation and maintenance accuracy of participating lab. The programme is conducted in Room – 156, Haematology Deptt., 1st floor, Cancer Hosp., AIIMS, New Delhi-110029