Annual index
Article Outline
Author index
Alberio, L., 48, 75
Baum, C., 303
Binet, J.L., 191
Budde, U., 83
Caporaso, N., 201
Cavazzana-Calvo., M., 272
Chiorazzi, N., 207
Cooke, B.M., 173
Coppel, R.L., 173
Delaunay, J., 165
Dong, J.-f., 15
Dunbar, C.E., 255, 257
Eber, S., 118
Eichhorst, B.F., 224
Fehse, B., 303
Ferrarini, M., 207
Fischer, A., 272
Fontana, S., 48
Fujimura, Y., 68
Gallagher, P.G., 142
George, J.N., 1, 60
Girma, J.-P., 41
Goldin, L., 201
Gribben, J.G., 246
Hacein-Bey-Abina, S., 272
Hallek, M.J., 224
Hassenpflug, W., 83
Hillmen, P., 192
Houlston, R., 192
Hovinga, J.A.K., 75
Ishizashi, H., 68
Kelly, P., 303
Kokame, K., 34
Kremer Hovinga, J.A., 48
Lämmle, B., 1, 48, 75
Larochelle, A., 257
Layh-Schmitt, G., 303
López, J.A., 15
Lozier, J., 287
Lundin, J., 234
Lux, S.E., 118
Marti, G.E., 201
Matsumoto, M., 68
Miyata, T., 34
Moake, J.L., 4
Mohandas, N., 91, 93, 173
Obser, T., 83
Österborg, A., 234
Persons, D.A., 279
Plaimauer, B., 24
Rai, K.R., 189
Rawstron, A., 192
Reid, M.E., 93
Rizouli, V., 246
Scheiflinger, F., 24
Schmidt, M., 303
Schneppenheim, R., 83
Studt, J.-D., 48, 75
Taleghani, B.M., 48
Terrell, D.R., 60
Tisdale, J.F., 279
Vesely, S.K., 60
Veyradier, A., 41
von Kalle, C., 303
Wada, H., 68
Walsh, C.E., 297
Wendtner, C.-M., 224
Yagi, H., 68
Subject index
AAV (adeno-associated virus vectors), 260
ABO blood group system, 94, 97, 109
Activation-induced cytosine deaminase (AID), 194–195
ADA deficiency gene therapy, 275, 306–307
ADAMTS-13
in acquired TTP-HUS, 9, 70–73
assays, 68–69
comparison of, 45–46
description of, 42–45
in diagnosis of thrombotic microangiopathies, 76–80
in idiopathic TTP-HUS, 64–65
limitations of, 9–10
cleavage site, 20
cleaving activity, 17
in congenital TTP-HUS, 69–70
C-terminal processing, 27
deficiency, 29
acquired due to autoantibodies, 85–86
clinical manifestations in children, 84–86, 88
conditions associated with, 84
conditions with, 84
hereditary, 86–87
indications for determining, 88–89
laboratory parameters, 86, 88
molecular pathology, 86–87
in TTP, 5–9, 76–80
docking to ULVWF substrate, 19–20
domain structure, 25–26, 42
electrophoresis, 42–44
in familial TTP, 8–9
functional, 34–35
in healthy adults, 9
identification of, 24–25, 84
infusions, for TTP, 10–11
recombinant human
in acquired/congenital TTP, 29–30
expression in mammalian/insect cells, 26–28
protease activity, 28
substrate specificity, 28
structural properties, 34
structure-function relationship, 28–29
ULVWF processing, 15
ADAMTS13 gene
mutations, 28–29, 84, 85
frameshift, 36
frequency of, 36–37
future issues, 37, 39
missense, 35
nosense, 35–36
splice, 36
sequencing methods, 37, 38
structure, 25
ADAMTS-13 inhibitor assays, 45
Adenamine deaminase deficiency gene therapy, 275, 306–307
Adeno-associated virus vectors (AAV), 260
Adenoviruses, 260
Adhesion proteins, erythrocyte membrane proteins as, 105–107
African-Americans, TTP-HUS development and, 61
Age, CLL incidence and, 197–198, 201
AID (activation-induced cytosine deaminase), 194–195
Alemtuzumab
for B-CLL, 235–237
development, 235
for minimum residual disease, 237
toxicity, 237–238
for T-PLL, 237
Alkylating agents, for CLL, 224–225
Anemia
in hereditary spherocytosis, 122
in malaria, 181
sickle cell. See Sickle cell disease
Animal models
of familial chronic lymphocytic leukemia, 204
fetal sheep xenotransplant, 262
of hemophilia, 287–290
of hereditary elliptocytosis, 153
of hereditary spherocytosis, 136–137
large, 263
nonhemophila, for testing gene transfer vectors, 290
primate, 263
of sickle cell anemia, 280–281
of β-thalassemia, 280–281
Anion transport, Diego blood group system and, 100–101
Ankyrin mutations, in hereditary spherocytosis, 128–130, 136
Antibiotic prophylaxis, after splenectomy, 127–128
Antibodies
blood group system, 93
monoclonal. See Monoclonal antibodies
Anti-CD5, 240
Anti-CD23, 240
Anticipation phenomenon, 203
Antigens, blood group
expression pattern, 95
function, structure, distribution and disease associations, 96–97
functions, 93–95
infectious diseases and, 110
natural “knockouts” in humans, 95, 98
ontogeny, 95
terminology, 95
Anti-HLA-DR, 240
APC gene, 193
Apolizumab, 240
Aquaporins, 103
Autoimmune disorders, TTP-HUS and, 63, 72
Bacterial receptors, erythrocyte membrane proteins as, 103–104
Band 3
defects, in hereditary spherocytosis, 130
GPA and, 104–105
lipid interactions, lack of, 134
mutations, clinical variability of, 136–137
B-cell chronic lymphocytic leukemia (B-CLL). See Chronic lymphocytic leukemia
B-cell receptor (BCR)
mediated signals, heterogeneity of, 210–211
repertoire, 209–210, 215–217
structure/function, 208–209
B cells
malignant. See Chronic lymphocytic leukemia, malignant B cells
monoclonal expansions in normal individuals, 217
subgroups, 214–215
B-CLL (B-cell chronic lymphocytic leukemia). See Chronic lymphocytic leukemia
BCR. See B-cell receptor
Bendamustine, for CLL, 229
Blood group systems. See also specific blood group systems
antibodies, 93
antigens. See Antigens, blood group
disease associations, 96–97
function/structure and distribution, 96–97
genes, 93
BRCA1 gene, 193
Bryostatin 1, 229
Calcineurin, thrombotic microangiopathy and, 5
Carbohydrates, in erythrocyte membrane, 95
Carrier state
hereditary elliptocytosis, 151
hereditary spherocytosis, 121
Cation cytoplasmic concentrations, in hereditary stomatocytoses, 167
CD34+, 255
CD20 antigen, 238
CD52 antigen, 235
CD38 expression, in CLL, 208, 214
Chemotherapy, for CLL
alkylating agents, 224–225
bendamustine, 229
combination with purine analogues, 225–229
hematopoietic growth factors, 229–230
historical aspects, 224
purine analogues, 225
Chido/Rodgers blood group system, 94, 97, 108–109
Chlorambucil, for CLL, 224
Chromosome abnormalities, in CLL, 192
Chronic lymphocytic leukemia (B-CLL)
age of onset, 197–198
BCR. See B-cell receptor
chromosome abnormalities, 191
classification, 207
clinical classifications, 189, 191, 201
clinical features, 207
cytogenic lesions in, 213
demographic patterns, 201
environmental factors, 201–202
epidemiology, 201–202
etiology, 204
future investigations, 204
genetics, 202–204
growth mechanisms, 211–212
indolent v aggressive forms, 196–197
inherited susceptibility, 192–193, 197. See also Familial chronic lymphocytic leukemia
malignant B cells
activation markers, 212
clonal evolution of, 212–214
maturation of, 212
surface characteristics, 217–218
sustained growth, in vivo, 211–212
telomere length, 212
in vivo turnover, 212–213
molecular monitoring of, 247–248
monoclonal B-cell lymphocytosis and, 194, 196
patient management decisions, 191
phenotype, 195–196
preleukemic cells, clonal evolution of, 214–217
prognosis, 246–247
immunoglobulin gene mutations, 191
markers of, 208
somatic mutations in immunoglobulin heavy-chain, 201
risk factors, 193, 197
staging, 246–247
subclinical
detection of, 194–195
prevalence of, 197–198
treatment, 191–192
alemtuzumab, 235–237
chemotherapy. See Chemotherapy, for CLL
monoclonal antibodies, 234–242
rituximab, 238–239
stem cell transplantation, 246–251
V gene subgroups, 208–210
Cladribine, for CLL, 225
Classification
of chronic lymphocytic leukemia, 189, 191, 201
of hereditary elliptocytosis, 150–152
CLL. See Chronic lymphocytic leukemia
Clonal heterogeneity, in immunoglobulin gene, 194–195
Clonality assessment, 194
Clonal selection, 309
Clones, gene-marked, evaluating for malignant potential, 313–314
Clopidogrel (Plavix), TTP development and, 5
Collagen-binding assay
for ADAMTS-13 inhibitors, 45
loss of high-molecular weight multimers of VWF, 44, 46
Colony-forming cell assays, 261
Colton blood group system, 94, 96, 102–103
Coombs test, in ADAMTS-13 deficiency, 86
Cord blood gene therapy, for ADA deficiency, 306–307
Cromer blood group system, 94, 97, 108
Cryohydrocytosis
hereditary type 1, 168–169
hereditary type 2, 170
Cyclophosphamide, for CLL, 224–225
Cytoadherence, in malaria infected red blood cells, 178–180
Cytokines, 263, 312
Deformability index (DI), 143
Dehydrated hereditary stomatocytosis, 167–168
Denileukin diftitox, 240
Depsipeptide (FR901228), 229
DHFR (dihydrofolate reductase), 266
DI (deformability index), 143
Diarrhea-associated HUS, 63
Diego blood group system
anion transport and, 100–101
description of, 94, 96
Dihydrofolate reductase (DHFR), 266
DNA transposons, 261
Dombrock blood group system, 94, 97, 107–108
Doxorubicin combination chemotherapy, for CLL, 225, 227, 228
Drug-associated TTP-HUS, 63, 72
Drug-resistance genes, 266
Duffy blood group system, 94, 96, 103–104, 174
EBV (Epstein-Barr viruses), 260
Ektacytometry, osmotic gradient, 143, 166
Elliptocytosis, hereditary, 142–156
alpha-spectrin alleles, low-expression of, 148–149
classification, 150–152
clinical severity, molecular determinants of, 154–155
clinical syndromes, 150
common, 151
differential diagnosis, 154
with dyserythroiesis, 152
genetic defects in, 145
with hemolysis, 151
homozygous and compound, 151–152
with infantile poikilocytosis, 152
inheritance/genetics, 142
laboratory characteristics, 153–154
malaria and, 154
mild or typical, 151
models of, 153
pathophysiology, 142–143
prevalence, 142
protein 4.1R mutations, 149–150
silent carrier state, 151
spectrin defects, 146–148
spherocytic, 152–153
with sporadic hemolysis, 151
treatment, 154
Endothelial cell-associated ULVWF strings, 8
anchorage, 19
character of, 17–19
formation, 17
TTP and, 8, 21–22
Endothelial cell surface, ULVWF localization, advantages of, 20–21
Engraftment, gene therapy, 308
Environmental factors, in CLL, 201–202
Enzymes, erythrocyte membrane proteins as, 107–108
Epirubicin combination chemotherapy, for CLL, 225, 227, 228
Epratuzumab, 240
Epstein-Barr viruses (EBV), 260
Erythrocyte membrane proteins, 93. See also Antigens, blood group
as adhesion proteins, 105–107
as enzymes, 107–108
in hereditary spherocytosis, 124
malaria parasite-induced modifications, 180–181
as receptors, 103–104
regulatory, and complementary elements, 108–110
solubilized, electrophoretic separation of, 143
with structural and transport function, 99–102
with structural function, 98–99
trafficking in malaria infected red cells, 178
with transport function, 102–103
Erythrocytes
cytoplasm alterations in malaria, 175–178
deformability, loss of, 134
malarial parasite invasion of, 173–175
membrane. See also Erythrocyte membrane proteins
composition/structure, 95
loss of surface by vesiculation, 133–134
pathobiology, in Southeast Asian ovalocytosis, 155
skeleton alterations in malaria, 175–178
thermal sensitivity, 144
Ethnicity, CLL incidence and, 201
Evans syndrome, 85, 86
Factor IX, immune response to, 290–291
Factor IX knockout mice, 288
Factor VIII, immune response to, 290–291
Factor VIII knockout mice, 288
Familial adenomatous polyposis (FAP), 193
Familial chronic lymphocytic leukemia
age of onset, 197–198
anticipation, 203
candidate genes, 204
carrier status, 197
family studies, 202–203
future investigations, 204
gene identification in, 193–194
migration studies, 203–204
model systems, 204
population studies of families, 203
precursor state, 204
Familial clustering, 193
Familial pseudohyperkalemia, 167
Fanconi anemia gene therapy, 312–313
FAP (familial adenomatous polyposis), 193
Fetal sheep xenotransplant models, 262
Fetus, spherocytic elliptocytosis in, 153
Fibronectin, 263–264
Flavopridol, 229
Flow cytometric assay, for subclinical CLL, 195–196
Fludarabine, for CLL
in combination chemotherapy, 225–229
with G-CSF, 229–230
single-agent, 225
“Founder effect,” 142
FR901228 (depsipeptide), 229
Fresh frozen plasma replacement, for TTP. See Plasma therapy, for TTP
FYB gene mutation, 104
G3139 (oblimersen), 229
Gallstones, in hereditary spherocytosis, 122
GALV envelope protein, 264
Gasser’s triad, 68
Genesense (oblimersen), 229
Gene therapy
ADA deficiency, 275
adverse events, 274–275
engraftment, 308
expansion of transformed clones, 308
hematopoietic stem cells as targets, 257
for hemoglobin disorders. See Hemoglobin disorders, gene therapy
for hemophilias. See Hemophilia gene therapy
for immunodeficiency diseases. See Immunodeficiency disease gene therapy
insertional mutagenesis in, 307–308
likelihood of transformation, 307–308
risks, 312–313
T-cell immunodeficiencies, 275–278
transgene coding sequences, 310
vectors. See Vectors, gene therapy
viral vectors, 258–260
Genetic defects. See also Mutations; specific genetic disorders
anticipation phenomenon, 203
in hereditary elliptocytosis, 142, 145
in malaria, 181–182
Southeast Asian ovalocytosis, 156
Gene transfer, 273–274
cell type, impact of, 309–310
initial clinical trials, 261–262
insertion site analysis, 306
by RNA trans-splicing, 297–299
by small interfering RNAs, 301
into stem cells, 257–261
future directions, 267–268
for hemoglobin disorders, 280
improvement, strategies for, 263–267
nonviral, 261
preclinical models, 262–263
viral, 258–260
Gerbich blood group system, 94, 96, 98–99
GFP gene, 265
γ-Globin vectors, 281
Gilbert syndrome, 166
GIL blood group system, 94, 96, 103
β-Globin locus control region, 280–281
β-Globin vectors, 281
Globoside blood group system, 94, 97, 109
Glycerol transport, GIL blood group system and, 103
Glycophorins
band 3 and, 104–105
Gerbich blood group system and, 98–99
GPC deficiency, 150
Glycoproteins, immunoglobulin superfamily of, 105–106
Growth factors, ex vivo stimulation of stem cells, 263
Heavy-chain gene rearrangement analysis, in detecting subclinical CLL, 194
HELLP, 62, 76
Hematopoiesis, lMO2 gene locus in, 304
Hematopoietic growth factors, for CLL, 229–230
Hematopoietic stem cells (HSCs). See Stem cells, hematopoietic
Hemoglobin disorders
etiology, 279
gene therapy, 256
achieving therapeutic cell levels, 283–284
chromosomal position effects, 281–283
detrimental chromosomal position effects, 281–283
using lentiviral vectors, 280–281
Hemolysis, with hereditary elliptocytosis, 151
Hemolytic-uremic syndrome (HUS)
acquired, 5, 70
alternative diagnoses and, 63–64
clinical features, 68, 76
clinical outcomes, 65–66
decreased VWF-CP in, 84
diarrhea-associated, 63
differential diagnosis, 68
drug-associated, 63
idiopathic, 64–65
pregnancy and, 62–63
v TTP, 83
Hemophilia gene therapy, 256
animal models, 287–290
immunity to transgene products, 290–291
immunity to vectors, 290
preclinical tests, 291–293
future directions/obstacles, 294–295
hemophilia A
clinical trials, 293–294
preclinical tests, 291–292
hemophilia B
clinical trials, 294
preclinical tests, 292–293
Herbicides, CLL and, 202
Hereditary disorders. See specific hereditary disorders
Hereditary pyropoikilocytosis (HPP)
alpha-spectrin alleles, low-expression of, 148–149
clinical features, 152
laboratory characteristics, 153–154
mutations, 143
thermal sensitivity of red blood cells and, 144
Herpesvirus vectors, 260
HFV (human foamy virus), 260
HIV-based vectors, 259–260, 265, 280
HIV infection, TTP-HUS and, 63
HOXB4, 267
HPP. See Hereditary pyropoikilocytosis
Hu1D10, 240
Human foamy virus (HFV), 260
HUS. See Hemolytic-uremic syndrome
Hypercholesterolemia, pseudo-homozygous with abnormal platelets, 170
Hypertrophic gastritis, with stomatocytosis, 170
IL-7Rα deficiency gene therapy, 275
Immunity
to gene therapy vectors, 290
to transgene products, 290–291
Immunoblotting with SDS-agarose gel electrophoresis, ADAMTS-13, 43–44, 46
Immunodeficiency disease gene therapy, 272–276
adverse events, 274–275
future prospects, 276
general considerations, 272–273
gene transfer technology and, 273–274
Immunoglobulin gene, clonal heterogeneity, 194–195
Immunoglobulin heavy-chain gene mutation, CLL outcome and, 191
Immunoglobulin superfamily, of glycoproteins, 105–106
Immunoradiometric assay, of VWF, 44–45, 46
Immunotoxins, monoclonal antibodies and, 241
Indian blood group system, 94, 96, 105
Infantile poikilocytosis, with hereditary elliptocytosis, 152
Infectious diseases, blood group antigens and, 110
Inherited diseases. See also specific inherited diseases
RNA repair of, 299–300
susceptibility to CLL, 192
Insertional mutagenesis
in gene therapy, 307–308
with replication competent retroviruses, 305–306
154InsLeu mutation, in α-spectrin repeat 2, 146–147
Integrinαvβ3, 19
Interleukins, B-CLL growth and, 211
JAK-3 disease gene therapy, 275
Japanese TTP-HUS experience
acquired disorders, 70–73
congenital/familial disorders, 69–70
methods/patients, 68–69
JMH blood group system, 94, 96, 107
Kappa:lambda ratio, 194
Kell blood group system, 94, 97, 107
Kidd blood group system, 94, 96, 102
Knockout mice, as hemophilia models, 287–288
Knops blood group system, 94, 97, 108
Kx blood group system, 94, 96, 101–102
Lactic dehydrogenase (LDH), in thrombotic microangiopathies, 4–5
LAD (leukocyte adhesion deficiency), 276
LAM-PCR, insertion site analysis, 306
LDH (lactic dehydrogenase), in thrombotic microangiopathies, 4–5
Lentiviral-based vectors
in animal models, 265
clinical trials, absence of, 268
description of, 259–260
for hemoglobin disorder gene therapy, 280–281
Leukocyte adhesion deficiency (LAD), 276
Lewis blood group system, 94, 97, 109
Ligand receptors, erythrocyte membrane proteins as, 103–104
Light-chain restriction analysis, in detecting subclinical CLL, 194
Linear amplification mediated polymerase chain reaction, 255
Linkage analysis, CLL, 194
lMO2 gene locus
in hematopoiesis, 304
insertional activation, 304
LMO2 promoter, 304–305
Low-affinity nerve growth factor receptor (LNGFR), 266
Lumiliximab, 240
Lutheran blood group system, 94, 96, 106
LW blood group system, 94, 96, 106
Malaria, 173–183
anemia in, 181
cytoplasm and membrane skeleton alterations, 175–178
Duffy-binding protein and, 103–104, 174
etiology, 173
genetic disorders in, 181–182
hereditary elliptocytosis and, 154
host-parasite relationship, 181–182
infected red blood cells, adhesive interactions in, 178–180
parasite-induced modifications of erythrocyte membrane proteins, 180–181
parasite invasion, 173–175
prevalence, 173
protein trafficking in infected red cells, 178
resistance, in Southeast Asian ovalocytosis, 156
rosetting, 180
symptoms, 173
Malignancy, hematological
corrective gene or site insertion determination, 313
with secondary TTP, 72
MBL. See Monoclonal B-cell lymphocytosis
McLeod syndrome, 101–102
Merozoites, 173–174
MGMT, 266
MGUS, myeloma and, 196
Minimum residual disease, eradication, alemtuzumab for, 237
Mitomycin C, thrombotic microangiopathy and, 5
Mitoxantrone, in combination chemotherapy for CLL, 225, 227
MMLV (Moloney murine leukemia virus vectors), 258–259
MNS blood group system, 94, 96, 104–105
Moloney murine leukemia virus vectors (MMLV), 258–259
Monoclonal antibodies
apolizumab, 240
epratuzumab, 240
future prospects, 241–242
immunotoxins and, 241
lumiliximab, 240
radioimmunotherapy, 240–241
rituximab, 238–239
T101, 240
target antigens, 234–235, 238
Monoclonal B-cell lymphocytosis (MBL)
age of onset, 197–198
CLL and, 194, 196
Moschcowitz’s pentad, 68
Murine xenotransplant models, 262–263
Mutations
ADAMTS13 gene. See ADAMTS13 gene, mutations
ankyrin, in hereditary spherocytosis, 128–130, 136
in hereditary pyropoikilocytosis, 143
154InsLeu, in α−spectrin repeat 2, 146–147
protein 4.1R, in hereditary elliptocytosis, 149–150
Myeloma, MGUS and, 196
Neonates
hereditary spherocytosis in, 121–122
spherocytic elliptocytosis in, 153
NK-cell subset reconstitution, 274
NOD/SCID, 26
“Nurse-like cells,” 191
Obesity, TTP-HUS development and, 61
Oblimersen (G3139; Genesense), 229
Ok blood group systems, 94, 96, 107
Oklahoma TTP-HUS registry
ADAMTS-13 analysis, 64–65
adverse effects of plasma exchange, 52
clinical categories, 61, 62–64
clinical outcomes, 65–66
data collection, 61
outcomes, clinical, 61
patient follow-up, 61
patient registration, 60
plasma exchange treatment, 61
results/discussion, 61–64
Oncovirinae, 258–259
Osmotic fragility test, in hereditary elliptocytosis, 153
Overhydrated hereditary stomatocytosis, 169–170
Parasite receptors, erythrocyte membrane proteins as, 103–104
PCR
heavy-chain gene rearrangement analysis, 194
insertion site analysis, 306
Pentostatin, for CLL, 225
Peripheral blood smear, in hereditary elliptocytosis, 153
Pesticides, CLL and, 202
Phagocyte cell disorders, 278
Phosphatase inhibitors, Ca2+-activated, 5
Plasma therapy, for TTP
adverse reactions, 51–52
Bern experience with, 52–57
current state of, 49
exchange, 11, 30–31
discontinuation of, 50
Oklahoma TTP-HUS registry, 61
optimal regimen, 50
survival rates and, 76
v infusion, 49–50
future directions, 30–31
historical development, 48–49
infusion, 30–31
for hereditary ADAMTS-13 deficiency, 87
v exchange, 49–50
optimal replacement fluid for, 50–51
Plasmodium falciparum, 173. See also Malaria
Platelet count, in TTP, 5
Platelet glycoprotein Ib-IX-V complex, interaction VWF, 16–17
Platelets
abnormal, with pseudo-homozygous hypercholesterolaemia, 170
aggregation, ULVWF-induced, 24
Plavix (clopidogrel), TTP development and, 5
Poikilocytosis, infantile with hereditary elliptocytosis, 152
Precursor states, malignant disease and, 196
Prednisone, with fludarabine for CLL, 228
Pregnancy
hereditary spherocytosis in, 121
secondary TTP, 72
spherocytic elliptocytosis in, 153
TTP-HUS and, 62–63
Primate models, 263
Prolymphocytic leukemia (PLL), 237, 251
Protein 4.1R
deficiency, etiology of, 150
in hereditary elliptocytosis, 149–150
qualitative defects, 150
quantitative defects, 149–150
structure/isoforms, 149
Protein 4.2R, in hereditary spherocytosis, 130–131
Proto-oncogenes, transcriptional activation, 307–308
Provirus, 258
P-selectin, 19
Pseudo-homozygous hypercholesterolaemia with abnormal platelets, 170
Pseudohyperkalemia, familial, 167
Pseudotyping, 264–265
Purine analogues, for CLL
in combination chemotherapy, 225–229
single-agent, 225
Quinine, thrombotic microangiopathy and, 5
Race, TTP-HUS development and, 61
Radiation exposure, leukemia and, 201–202
Radioimmunotherapy, 240–241
Raph blood group system, 94, 97, 109–110
RD114 envelope protein, 264
Recombinant fusion protein, 240
Red blood cells. See Erythrocytes
Red cell indices, 165–166
Replication-competent retrovirus-contaminated vector stocks, 263
Retronectin, 264, 265
Retroviral vectors, 261–262
with drug-resistance genes, 266
gene transfer
for Fanconi anemia, 312–313
for hemoglobin disorders, 280
side effects, 303–304
success, 303–304
human foamy virus, 260
improvements, future opportunities for, 309
integration preferences, 305
lentiviruses, 259–260
life cycle, 258
oncoretroviruses, 258–259
pseudotyping, 264–265
replication competent, insertional mutagenesis studies, 305–306
transgene architecture, 308–309
Rh blood group system, 94, 96, 102
Rituximab
in B-CLL, 238–239
development, 238
toxicity, 239
RNA-cis-splicing, 297–298
RNA-trans-splicing, 297–299
efficiency/specificity of, 300–301
repair of inherited disease, 299–300
types, 299, 300
Rosetting, malarial, 180
SAO. See Southeast Asian ovalocytosis
SB transposon (Sleeping Beauty transposon), 261
Scianna blood group system, 94, 96, 107
SCID. See Severe combined immunodeficiencies
SCID-repopulating cells (SRC), 262
SDS-agarose gel electrophoresis, ADAMTS-13, 43–44, 46
SDS-PAGE
degraded VWF substrate, 43–44, 46
erythrocyte membrane proteins, 143
erythrocyte membrane proteins in hereditary spherocytosis, 124
Self-association, of spectrin dimers, 144
Self-inactivating-type transfer vectors, 259–260
Severe combined immunodeficiencies (SCID)
ADA deficiency, 272
gene therapy for, 272–273
retrovirus gene therapy for, 303–304
X-linked. See X-SCID gene therapy
Sickle cell disease
etiology, 279
gene therapy, 256
achieving therapeutic cell levels, 283–284
chromosomal position effects, 281–283
using lentiviral vectors, 280–281
palliative therapy, 279
Sleeping Beauty transposon (SB transposon), 261
Small interfering RNAs (siRNAs), 301
Southeast Asian ovalocytosis (SAO)
classification, 150
clinical characteristics, 156
etiology, 100–101
genetic defects, 156
malaria resistance, molecular basis for, 156
membrane pathbiology, 155
Spectrin
alpha alleles, low-expression of, 148–149
defects, 143–149
α-defects in repeats 2 to 5, 146–147
in hereditary spherocytosis, 131–132
mutations, 136, 143
remote from αβ−spectrin self-association site, 147–148
deficiency, severity of hereditary elliptocytosis and, 154–155
self-association, 143
contact site mutations, 145–146
in vitro studies, 144
structure, 142–143
thermal sensitivity, 144
tryptic peptide mapping of, 144
Spherocytic elliptocytosis, 152–153
Spherocytosis, hereditary, 118–137
animal/fish models, 136–137
carrier state, 121
classification, severity-based, 119–122
clinical presentation, 119–122
complications, 122
diagnostic findings, 123
differential diagnosis, 123–124
etiology, 128–132
genetics, 118–119
membrane protein composition, measuring, 124
molecular defects, 124–125, 128–132
molecular screening method, 132–133
pathophysiology, 133–136
prevalence, 118
sequestration in spleen, 134–135
treatment, 125–128
Spinoculation, 263–264
Splenectomy
for hereditary elliptocytosis, 154
for hereditary spherocytosis, 125–128
Splenic conditioning, 135
Spumavirus-derived vectors, 260, 268
Stem cells, hematopoietic. See also Stem cell transplantation
alternative sources, 263
ex vivo stimulation with cytokines, 263
transduction, 257, 267–268
nonstimulatory culture conditions after, 265
positive selection methods, 265–267
strategies for improving, 263–267
Stem cell transplantation
for CLL
allogeneic, 249–250
autologous, 248–249
identification of poor risk patients, 246–247
limitations on, 246
nonmyeloablative, 250–251
rationale for, 247–248
timing of, 248
for prolymphocytic leukemia, 251
TTP associated with, 72
for TTP-HUS, 62
Stomatin
EPB72 gene, 169
in hereditary type 1 cryohydrocytosis, 168–169
pre-messenger, abnormal splicing of, 170
reduced, in hereditary type 2 cryohydrocytosis, 170
structure, 169
Stomatocytosis, hereditary, 165–170
with abnormal platelets, and pseudo-homozygous hypercholesterolaemia, 170
cryohydrocytoses, 168–169, 170
dehydrated, 167–168
diagnostic testing, 165–167
historical aspects, 165
with hypertrophic gastritis, 170
overhydrated, 169–170
unique multisystem, 170
Subtotal splenectomy, for hereditary spherocytosis, 126–127
T101, 240
Target antigens, for monoclonal antibody therapy
CD20, 238
T-cell immunodeficiency diseases, gene therapy for, 272–273, 275–278
T-cell prolymphocytic leukemia (T-PLL), 237, 251
Temperature dependence of leak, in hereditary stomatocytoses, 167
TERT activity, 310
β-Thalassemia
etiology, 279
gene therapy, 256
achieving therapeutic cell levels, 283–284
detrimental chromosomal position effects, 281–283
lentiviral vector-based, 280–281
palliative therapy, 279
Thermal sensitivity, of red blood cells and spectrin, 144
Thrombotic microangiopathies. See also Thrombotic thrombocytopenic purpura
bone marrow transplantation-associated, 9
diagnosis, ADAMTS-13 assays in, 76–80
drug-induced, 5
historical aspects, 75
Thrombotic thrombocytopenic purpura (TTP)
acquired, 9, 29–30, 70–71
ADAMTS-13 deficient types, 5–9
ADAMTS13 sequence analysis, 37–38
alternative diagnoses and, 63–64
autoimmune disorders and, 63
clinical features, 34, 68
clinical outcomes, 65–66
differential diagnosis, 68
drug-associated, 63
familial or congenital, 5, 69–70. See also ADAMTS13 gene
ADAMTS-13 activity, 8
historical aspects, 83–84
rADAMTS-13 in, 29–30
treatment, 11
in future, 11–12
historical aspects, 4
idiopathic, 64–65, 68, 71–72
incidence, 75
pregnancy and, 62–63
secondary, 68, 72
treatment
hematopoietic stem cell transplantation, 62
plasma therapy. See Plasma therapy, for TTP
with rADAMTS-13, 29–30
signs/symptoms, 5
treatment, 10–11
types of, 4–5, 75
ULVWF strings in, 15, 21–22
Ticlopidine (Ticlid), TTP development and, 5
Total body irradiation, thrombotic microangiopathy and, 5
T-PLL (T-cell prolymphocytic leukemia), 237, 251
Transcriptional activation, mutagenesis, 307–308
Transfusion-related acute lung injury (TRALI), 51, 52
Transgene
architecture, 308–309
classification, 310–311
coding sequences, 310
nonphysiologic expression, 310–312
Tryptic peptide mapping, of spectrin, 144
TTP. See Thrombotic thrombocytopenic purpura
UCN-01, 229
Ultralarge multimers of von Willebrand factor (ULVWF)
cleavage by ADAMTS-13, 7–8, 12
docking of ADAMTS-13 to, 19–20
in familial TTP, 83–84
interaction with platelet glycoprotein Ib-IX-V complex, 6, 16–17
localization to endothelial cell surface, advantages of, 20–21
platelet aggregation, 24
self-association, 18–19
strings. See Endothelial cell-associated ULVWF strings
in TTP, 5–6, 15
Upshaw-Schulman syndrome, 75–76
Urea transport
GIL blood group system and, 103
Kidd blood group system and, 102
Vector envelope proteins, modification of, 264–265
Vectors, gene therapy, 290. See also specific vectors
improvements, future opportunities for, 309
insertion, frequency of, 307
Venous thromboembolism, from plasma exchange, 52
Very-late antigens (VLAs), 264
Vesticular stomatitis virus-protein, 264
V gene subgroups, f CLL, 208–210
Viral receptors, erythrocyte membrane proteins as, 103–104
Viral vectors, 258–260
Virus envelopes, novel, 264–265
VLAs (very-late antigens), 264
von Willebrand factor (VWF)
degraded substrate, SDS-PAGE analysis of, 43–44, 46
A domains, 19–20
endothelial release of, 17, 41–42
endothelial surface binding, 17
interaction with platelet glycoprotein Ib-IX-V complex, 16–17
loss of high-molecular weight multimers, 43, 44, 46
metabolism, 6–9
multimers, 6, 15, 41. See also Ultralarge multimers of von Willebrand factor
residual
functional measurement of, 44, 46
immunological measurement of, 44–45, 46
storage, 15–16
strings. See Endothelial cell-associated ULVWF strings
substrate and enzyme properties, 41–42
synthesis, 15
Von Willebrand factor-cleaving protease (VWF-CP). See ADAMTS-13
WAS (Wiskott-Aldrich syndrome), 273, 278
Water transport
Colton blood group system and, 102–103
GIL blood group system and, 103
Weibel-Palade bodies, 15, 17, 19, 24
Wiskott-Aldrich syndrome (WAS), 273, 278
Xg blood group system, 94, 96, 107
X-SCID gene therapy
adverse events, 272, 274, 304
lMO2-associated, 268
retroviral, 259, 303–304
success, 304
Yt blood group system, 94, 97, 107
ZAP-70 expression, in CLL, 208, 214
PII: S0037-1963(04)00235-5
doi:10.1053/S0037-1963(04)00235-5
