RESUMEN
We document the characteristics of BCR-ABL kinase domain mutations (KDM) in the largest study from India comprising of 385 patients and demonstrate that more than half (51.9%) of these patients have detectable abnormalities in the KD both in adult and in pediatric chronic myelogenous leukemia (CML). These comprise singly occurring missense mutations (25.5%), polyclonal/compound point mutations (4.9%), and insertions/deletions (29.6%). Missense mutations were most commonly seen in the imatinib-binding region followed by the P-loop. The commonest mutation in our dataset was T315I. Other common missense mutations were Y253H, M244V, and F317L. A high prevalence of BCR-ABL exon7 deletion (p.R362fs*) was also seen (25.5% of the entire cohort), whereas the 35bpintron-derived insertion/truncation mutation detected in 12 patients. In the pediatric age group, 58.8% of patients harbored missense mutations, polyclonal/compound mutations as well as insertions and deletions. We detected 11 novel mutations (seven missense mutations and four insertions/deletions).
Asunto(s)
Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Mutación , Dominios y Motivos de Interacción de Proteínas/genética , Adolescente , Adulto , Anciano , Alelos , Niño , Resistencia a Antineoplásicos/genética , Femenino , Proteínas de Fusión bcr-abl/química , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Mutación INDEL , India/epidemiología , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/epidemiología , Masculino , Persona de Mediana Edad , Mutación Missense , Vigilancia de la Población , Pronóstico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
CONTEXT: Hairy cell leukemia (HCL) is a rare, low grade, B-cell neoplasm with a characteristic morphologic and immunophenotypic profile. It has to be distinguished from chronic lymphoproliferative disorders because of different treatment protocol and clinical course. AIMS: To evaluate clinicopathological features including immunophenotypic analysis of cases diagnosed as HCL. MATERIALS AND METHODS: The present study included 28 cases diagnosed over a period of nine years (2002-2010). Clinical presentation, complete blood count, bone marrow aspirate, and flow cytometric analysis of cases were reviewed. Treatment and follow-up details (ranging from 3-90 months) were noted. RESULTS: This study revealed 28 cases (referrals-7, indoor-21), aged 26-69 years with a median age of 47 years, with a male predominance (M:F=6:1). The presenting complaints were weakness (80%) followed by fever (56%) and abdominal pain. Physical examination revealed splenomegaly in most patients (92%) and hepatomegaly in a minority (28%). The common laboratory features were anemia in 23 cases, pancytopenia in 14 cases, while two patients had leukocytosis and three patients had normal WBC count. Dry tap was observed in 84% of the cases where hairy cells constituted 16-97% of non-erythroid nucleated cells. Tartarte resistant acid phosphate staining was positive in all the eight cases where it was done. CD5 was negative in all the cases, while CD10 was expressed in three cases (13%) and CD23 in five cases (19%). CONCLUSIONS: Though pancytopenia is common, occasional patient can present with normal blood counts or leukocytosis. Few unusual findings include presence of lymphadenopathy, absence of palpable splenomegaly, and expression of CD23 and CD10 by the leukemic cells.
Asunto(s)
Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/patología , Adulto , Anemia , Recuento de Células Sanguíneas , Médula Ósea/patología , Instituciones Oncológicas , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: We compared the international flow reference method (IRM) platelet counts with those obtained from CellDyn Sapphire (impedance and optical counts), LH750 (impedance counts), and the flowcytometry based ReaPanThrombo Immunoplatelet method (ReaMetrix). We further evaluated the degree of agreement of above methods with the IRM at the transfusion thresholds of 10 x 10(9) l(-1) and 20 x 10(9) l(-1). METHODS: A total of 104 thrombocytopenic blood samples with platelet count of <50 x 10(9) l(-1) were selected for the study. All samples were tested in parallel by various methods within 6 h of blood collection. RESULTS: For bias estimation, a Bland-Altman analysis was done by taking the IRM as the standard method. The bias for CDS-I counts was +6.505 x 10(9) l(-1) (95% LA -2.110 to +15.122), for CDS-O counts the bias was -3.779 x 10(9) l(-1) (95% LA -8.950 to +1.392), for LH750 the bias was +0.111 x 10(9) l(-1) (95% LA -5.862 to +6.084) and that for ReaMetrix was -1.602 x 10(9) l(-1) (95% LA -7.400 to +4.194). The LH750 had the least average bias and it overestimated platelet counts marginally. The ReaMetrix method showed the highest degree of agreement with the IRM, at both the threshold points with a K value of 0.960 (threshold < or = 10 x 10(9) l(-1)) and 0.923 (threshold < or = 20 x 10(9) l(-1)). CONCLUSIONS: Impedance platelet counts from LH750 were more accurate than optical methods in thrombocytopenic patients. ReaMetrix immunoplatelet counts show the maximum degree of agreement with the IRM at clinically relevant transfusion thresholds. We conclude that as current platelet transfusion thresholds are based on results of automated hematology analyzer methods, the true thresholds may be determined using the IRM and CD41/61 based single-platform immunoplatelet methods.
Asunto(s)
Citometría de Flujo/métodos , Internacionalidad , Recuento de Plaquetas/métodos , Juego de Reactivos para Diagnóstico , Trombocitopenia/sangre , Eritrocitos/patología , Humanos , Transfusión de Plaquetas , Estándares de ReferenciaRESUMEN
OBJECTIVE: Acute Leukemia is rare in infants. It is characterized by non-specific symptomatology requiring a high index of suspicion on the part of a pediatrician for referral and diagnosis. It has peculiar biological features, unresponsiveness to treatment and poor prognosis. METHODS: Eighteen infants with acute leukemia were seen during 1994 to 2001 and were analyzed on the basis of clinical and laboratory data. There were 13 cases of Acute Lymphoblastic Leukemia (ALL), 4 cases of Acute Myeloid Leukemia (AML) and one case remained unclassifiable, as the surface markers could not be done. Morphologically 9/13 cases of ALL were of FAB L1 type and remaining of L2 subtype, and 2/4 cases of AML were of FAB M1 type and remaining of M2 subtype. RESULT: Clinical data was available completely only in 11 cases. Hyperleucocytosis was present in 4 cases, organomegaly in 8 cases and lympadenopathy in 5 cases. One patient presented with a chloroma in the retrorbital region although there was no parenchymal involvement of the brain. Immunophenotyping could be done in 13 cases, where 7 cases were diagnosed as CALLA positive-ALL (HLADR+, CD19+, CD10+), 2 cases as Early Pre-B ALL (HLADR+, CD19+, CD10 negative), one as T ALL (cCD3+, CD2+, CD7+) and 3 cases as AML (CD13+, CD33+, HLADR+). None of our patients received treatment.