فهرست مطالب:

1 Techniques in Cytogenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2 Techniques in Molecular Hematology. . . . . . . . . . . . . . . . . . . . . 17
2.1 Polymerase Chain Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Part I Case Studies in Myeloid Malignancies
3 Acute Myeloid Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
3.1 Case Study 3.1: Acute Myeloid Leukemia
with t(8;21)(q22;q22.1);RUNX1-RUNX1T1
and KIT Gene Mutation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
3.2 Case Study 3.2: Acute Myeloid Leukemia
with a Variant Three-Way Translocation t(8;17;21)
(q22;q23;22.1);RUNX1-RUNX1T1 . . . . . . . . . . . . . . . . . . . 41
3.3 Case Study 3.3: Acute Myeloid Leukemia,
t(8;21)(q22;q22) with Rare Duplication of der (21) . . . . . . . 42
3.4 Case Study 3.4: AML with inv(16)
(p13;q22)/t(16;16)p(13;q22);CBFB–MYH11 . . . . . . . . . . . . 44
3.5 Case Study 3.5: Acute Myeloid Leukemia
with t(9;11)(p21;q23.3)(KMT2A-MLL3)
with Trisomies of Chromosomes 8 and 21 . . . . . . . . . . . . . . 46
3.6 Case Study 3.6: Acute Promyelocytic
Leukemia with PML-RARA, t(15;17)
with Mutated FLT3-TKD (D835) . . . . . . . . . . . . . . . . . . . . . 47
3.7 Case Study 3.7: Acute Promyelocytic Leukemia
with Variant (11;17)(q23;q21.1)(PLZF/RARA) . . . . . . . . . . 49
3.8 Case Study 3.8: Acute Promyelocytic Leukemia
with t(15;17) and t(9;22) Translocations, Trisomy 8
and Multiple Molecular Abnormalities . . . . . . . . . . . . . . . . . 51
3.9 Case Study 3.9: Acute Promyelocytic Leukemia
with PML-RARA t(15;17) with Mutated FLT3-ITD. . . . . . . 52
3.10 Case Study 3.10: Acute Myeloid Leukemia
with Normal Karyotype, Mutated NPM1 and FLT3-ITD . . . 54
3.11 Case Study 3.11: Acute Myeloid Leukemia
with normal Karyotype and NPM 1 Gene Mutation . . . . . . . 56
3.12 Case Study 3.12: Acute Myeloid Leukemia
with Normal Karyotype and FL3-ITD Gene Mutation . . . . . 58
3.13 Case Study 3.13: Acute Myeloid Leukemia
with t(11;19) and FLT3-ITD Mutation . . . . . . . . . . . . . . . . . 59
3.14 Case Study 3.14: t-Acute Myeloid Leukemia with
Myelodysplasia-Related Changes (AML-MRC)
with Monosomy 7 Transformed from Aplastic Anemia . . . . 60
3.15 Case Study 3.15: Acute Myeloid Leukemia
with Myelodysplasia-Related Changes
with Monosomy 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
3.16 Case Study 3.16: Acute Myeloid Leukemia
with Myelodysplasia-Related Changes
with Monosomal Karyotype . . . . . . . . . . . . . . . . . . . . . . . . . 63
3.17 Case Study 3.17: Acute Myeloid Leukemia
(s-AML) from (MDS-EB2) with
Myelodysplasia-Related Changes
with Complex Karyotype. . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
3.18 Case Study 3.18: Acute Myeloid Leukemia
(t-AML) with Myelodysplasia-Related Changes
with Monosomy 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
3.19 Case Study 3.19: Acute Myeloid Leukemia
with Myelodysplasia-Related Changes
with Complex Karyotype. . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
3.20 Case Study 3.20: Acute Myeloid Leukemia
with Myelodysplasia-Related Changes
(MDS-EB1) with Complex Karyotype . . . . . . . . . . . . . . . . . 70
3.21 Case Study 3.21: Acute Myeloid Leukemia
(t-AML) with t(11;19)(q23;p13.1)(KMT2A-ELL) . . . . . . . . 73
3.22 Case Study 3.22: Therapy-Related Acute
Myeloid Leukemia (t-AML)
with Hypodiploid Complex Karyotype . . . . . . . . . . . . . . . . . 74
3.23 Case Study 3.23: s-AML with Monocytic
Differentiation with der(1) t(1;15)(q11;q13)
Evolving from Polycythemia Vera . . . . . . . . . . . . . . . . . . . . . 77
3.24 Case Study 3.24: Acute Myeloid Leukemia
(s-AML) from Primary Myelofibrosis
with Complex Karyotype. . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
3.25 Case Study 3.25: Acute Megakaryoblastic
Leukemia with Isolated Deletion 9q . . . . . . . . . . . . . . . . . . . 82
3.26 Case Study 3.26: Acute Myeloid Leukemia,
NOS, with Isolated Trisomy 11 . . . . . . . . . . . . . . . . . . . . . . . 83
3.27 Case Study 3.27: Acute Myeloid Leukemia,
NOS with Isolated Trisomy 14 . . . . . . . . . . . . . . . . . . . . . . . 85
3.28 Case Study 3.28: Acute Myeloid Leukemia,
NOS with Sole Abnormality of Trisomy 8 . . . . . . . . . . . . . . 86
3.29 Case Study 3.29: Acute Myeloid Leukemia:
AML-M7 (NOS) with Complex Karyotype . . . . . . . . . . . . . 88
3.30 Case Study 3.30: Acute Myeloid Leukemia
with Lineage Switch from ALL with TP53
alterations and Complex Karyotype. . . . . . . . . . . . . . . . . . . . 89
3.31 Case Study 3.31: Acute Myeloid Leukemia
with Normal Karyotype and NPM1 Mutation
on (RT-PCR) with NPM1 and FLT3-ITD
Mutation on NGS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
3.32 Case Study 3.32: Acute Myeloid Leukemia
with t(8;21) and RUNX1-RUNX1T1 Gene
Rearrangement on RT-PCR and NGS . . . . . . . . . . . . . . . . . . 93
3.33 Case Study 3.33: Acute Myeloid Leukemia
with Normal Karyotype and NPM1 Mutation
on RT-PCR and NGS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Annexure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
4 Myelodysplastic Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
4.1 Case Study 4.1: Myelodysplastic Syndrome
(MDS-EB2) with Rare Interstitial Deletion
of the Long Arm of Chromosome 9. . . . . . . . . . . . . . . . . . . . 101
4.2 Case Study 4.2: Myelodysplastic Syndrome
with Excess Blasts (MDS-EB2) and Trisomy 8. . . . . . . . . . . 102
4.3 Case Study 4.3: Myelodysplastic Syndrome
with Multilineage Dysplasia (MDS-MLD)
with Monosomal Karyotype . . . . . . . . . . . . . . . . . . . . . . . . . 104
4.4 Case Study 4.4: Myelodysplastic Syndrome
with Multilineage Dysplasia (MDS-MLD)
with Deletion 13q. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
4.5 Case Study 4.5: Therapy Related Myelodysplastic
Syndrome with Complex Karyotype . . . . . . . . . . . . . . . . . . . 108
4.6 Case Study 4.6: Myelodysplastic Syndrome
with Excess Blasts (MDS-EB-2) with Dicentric
Chromosome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
4.7 Case Study 4.7: Myelodysplastic Syndrome
with Excess Blasts-EB1 (MDS-EB-1)
with Composite Karyotype . . . . . . . . . . . . . . . . . . . . . . . . . . 111
4.8 Case Study 4.8: Myelodysplastic Syndrome
(MDS-EB-2) with Monosomal Karyotype . . . . . . . . . . . . . . 114
4.9 Case Study 4.9: Myelodyaplastic Syndrome
with Isolated 5q Deletion (5q-Syndrome) . . . . . . . . . . . . . . . 116
Annexure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
5 Myelodysplastic/Myeloproliferative
Neoplasms (MDS/MPN) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
5.1 Case Study 5.1: Myelodysplastic Syndrome:
Myeloproliferative Neoplasm (CMML-1-RS). . . . . . . . . . . . 119
5.2 Case Study 5.2: Myelodysplastic Syndrome/
Myeloproliferative Neoplasm (CMML-2) with del (20q) . . . 122
5.3 Case Study 5.3: Myelodysplastic: Myeloproliferative
Neoplasm MDS-MPN-CMML-O with Rare t(2;11) . . . . . . . 124
5.4 Case Study 5.4: Myelodysplastic Syndrome:
Myeloproliferative Neoplasm CMML-1
with Isolated Trisomy 8 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
5.5 Case Study 5.5: Myelodysplastic Syndrome:
Myeloproliferative Neoplasm Atypical CML
(a CML) with i(17q). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
5.6 Case Study 5.6: Myelodysplastic Syndrome
Myeloproliferative Neoplasm (CMML-1)
with t(1;15) with Derivative Chromosome 15 . . . . . . . . . . . . 130
Annexure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
6 Myeloproliferative Neoplasms (MPNs). . . . . . . . . . . . . . . . . . . . 133
6.1 Case Study 6.1: Myeloproliferative Neoplasm:
Primary Myelofibrosis with Trisomy 9 . . . . . . . . . . . . . . . . . 133
6.2 Case Study 6.2: Myeloproliferative Neoplasm:
Polycythemia Vera with JAK 2 Mutation. . . . . . . . . . . . . . . . 135
6.3 Case Study 6.3: Myeloproliferative Neoplasm:
Primary Myelofibrosis with JAK2 Mutation . . . . . . . . . . . . . 135
6.4 Case Study 6.4: Myeloproliferative Neoplasm:
Essential Thrombocythemia with CALR Mutation . . . . . . . . 136
6.5 Case Study 6.5: Myeloproliferative Neoplasm:
Essential Thrombocythemia with JAK2 Mutation. . . . . . . . . 137
Annexure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
7 Chronic Myeloid Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
7.1 Case Study 7.1: Chronic Myeloid Leukemia
with Lymphoid Blast Crisis with Rare dic (7;9) . . . . . . . . . . 139
7.2 Case Study 7.2: Chronic Myeloid Leukemia
in Myeloid Blast Crisis with Hyperdiploid
Complex Karyotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
7.3 Case Study 7.3: Chronic Myeloid Leukemia
in Myeloid Blast Crisis with t(9;22) and inv(16). . . . . . . . . . 143
7.4 Case Study 7.4: Chronic Myeloid Leukemia
in Myeloid Blast Crisis with a Novel dic(16;17)
and TP53 Gene Deletion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
Annexure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
8 Next Generation Sequencing for Diagnostics
of Myeloid Malignancies for Routine Clinical Use:
Pitfalls and Advantages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
Reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
Part: II Case Studies in Lymphoid Malignancies
9 Acute Lymphoblastic Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . 151
9.1 Case Study 9.1: Acute Lymphoblastic Leukemia
with High Hyperdiploidy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
9.2 Case Study 9.2: Acute Lymphoblastic Leukemia
with Complex Karyotype with t(12;21) (ETV6/RUNX1) . . . 152
9.3 Case Study 9.3: Philadelphia Chromosome
Positive Acute Lymphoblastic Leukemia
with Hypodiploidy, Monosomy 7, and der 6 t(2;6) . . . . . . . . 154
9.4 Case Study 9.4 Acute Lymphoblastic Leukemia
with normal Karyotype with t(12;21) on FISH . . . . . . . . . . . 156
9.5 Case Study 9.5: Acute Lymphoblastic Leukemia
with t (1;19) (q23;p13.3) and i(1)(q10) . . . . . . . . . . . . . . . . . 158
9.6 Case Study 9.6: Acute Lymphoblastic Leukemia
with del(9p) and dup (1q) . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
9.7 Case Study 9.7: Relapsed Precursor B Acute
Lymphoblastic Leukemia with t(12;17)(p13;q11.2) . . . . . . . 161
9.8 Case Study 9.8: Philadelphia Chromosome
Positive Acute Lymphoblastic Leukemia
with High Hypodiploidy with Monosomy 7 . . . . . . . . . . . . . 163
9.9 Case Study 9.9: Therapy Related Acute
Lymphoblastic Leukemia with Complex Karyotype . . . . . . . 164
9.10 Case Study 9.10: Early T Cell Precursor
Acute Lymphoblastic Leukemia (ETP-ALL)
with Normal Karyotype and FLT3-ITD
Mutation Positive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
9.11 Case Study 9.11: Acute Lymphoblastic Leukemia
with del (9p). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
9.12 Case Study 9.12: Acute Lymphoblastic Leukemia
with High Hyperdiploidy with Complex Karyotype
and TP53 Gene Deletion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
9.13 Case Study 9.13: Acute Lymphoblastic Leukemia
with Complex Karyotype with t(4;11) (q21;q23) . . . . . . . . . 171
9.14 Case Study 9.14: Acute Lymphoblastic Leukemia
with both Hyperdiploid and Hypodiploid Clones . . . . . . . . . 173
9.15 Case Study 9.15: Philadelphia Chromosome
Positive Acute Lymphoblastic Leukemia
with additional Cytogenetic Abnormalities . . . . . . . . . . . . . . 175
9.16 Case Study 9.16: Acute Lymphoblastic Leukemia
with Masked t(9;22). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
9.17 Case Study 9.17: Philadelphia Chromosome
Positive Acute Lymphoblastic Leukemia. . . . . . . . . . . . . . . . 179
9.18 Case Study 9.18: Acute Lymphoblastic Leukemia
with der 19 t(1;19) (q23;p13). . . . . . . . . . . . . . . . . . . . . . . . . 180
9.19 Case Study 9.19: Acute Lymphoblastic Leukemia
with Philadelphia Chromosome t(9;22)(q34;q11.2)
with i(8)(q10)and der (5) t (5;8). . . . . . . . . . . . . . . . . . . . . . . 181
9.20 Case Study 9.20: Acute Lymphoblastic
Leukemia/Non-Hodgkin’s Lymphoma
with a Variant t(8;22), MYC/IGL. . . . . . . . . . . . . . . . . . . . . . 184
9.21 Case Study 9.21: Relapsed Philadelphia
Chromosome Positive Acute Lymphoblastic
Leukemia with Composite Karyotype and del(7p) . . . . . . . . 186
9.22 Case Study 9.22: Acute Lymphoblastic Leukemia
with Complex Karyotype. . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
9.23 Case Study 9.23: Acute Lymphoblastic Leukemia
with Eosinophilia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
Annexure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
10 Chronic Lymphocytic Leukemia
and Non-Hodgkin’s Lymphomas. . . . . . . . . . . . . . . . . . . . . . . . . 195
10.1 Case Study 10.1: Chronic Lymphocytic Leukemia
with ATM Gene (11q22) Gene Deletion
and Trisomy 12 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
10.2 Case Study 10.2: Chronic Lymphocytic
Leukemia with Isolated Trisomy 12 . . . . . . . . . . . . . . . . . . 197
10.3 Case Study 10.3: Chronic Lymphocytic
Leukemia with TP53 (17p13) and RB 1
(13q14) Gene Deletions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
10.4 Case Study 10.4: Chronic Lymphocytic
Leukemia with ATM (11q22) and RB 1
(13q14) Gene Deletions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
10.5 Case Study 10.5: Chronic Lymphocytic Leukemia
with IgH and Gene Rearrangement and Trisomy 12 . . . . . . 202
10.6 Case Study 10.6: Chronic Lymphocytic
Leukemia with Isolated RB 1 Gene Deletion (13q14). . . . . 204
10.7 Case Study 10.7: Chronic Lymphocytic
Leukemia with Partial deletion of IgH (14q32)
Gene Rearrangement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
10.8 Case Study 10.8: Chronic Lymphocytic Leukemia
with Biallelic and Monoallelic RB 1 Gene
Deletion (13q14) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206
10.9 Case Study 10.9: Chronic Lymphocytic Leukemia
with Sole Abnormality of ATM Gene
Deletion (11q22) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
10.10 Case Study 10.10: Leukemic Mantle Cell
Lymphoma with Rearranged IgH gene, t(11;14)
and Trisomy 12 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
10.11 Case Study 10.11: Chronic Lymphocytic
Leukemia with Trisomy 12 and RB1 (13q14)
Gene Deletion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
10.12 Case Study 10.12: Non-Hodgkin’s lymphoma
(Follicular Lymphoma)—Double-Hit Extra
Copy Lymphoma (Atypical Double-Hit Lymphoma) . . . . . 211
10.13 Case Study 10.13: Non-Hodgkin’s
Lymphoma—Double-Hit Diffuse Large
B Cell Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
10.14 Case Study 10.14: Non-Hodgkin’s
Lymphoma—Splenic Marginal Zone Lymphoma
with Extra Copies of MYC gene (NOS) . . . . . . . . . . . . . . . 216
10.15 Case Study 10.15: Non-Hodgkin’s
Lymphoma—Anaplastic Large Cells Lymphoma . . . . . . . . 218
10.16 Case Study 10.16: Non-Hodgkin’s
Lymphoma—Mantle Cell Lymphoma with t(11;14) . . . . . . 219
10.17 Case Study 10.17: Non-Hodgkin’s
Lymphoma—High-Grade B Cell Lymphoma
(NOS) with BCL-2 Extra Copies. . . . . . . . . . . . . . . . . . . . . 221
Annexure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
Part III Case Studies in Multiple Myeloma
11 Multiple Myeloma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
11.1 Case Study 11.1: Multiple Myeloma with IgH Gene
Rearrangement, t(11;14) . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
11.2 Case Study 11.2: Multiple Myeloma
with Partial Deletion of IgH Gene Rearrangement,
Monosomy Chromosome 13, Trisomy
Chromosome 11 and Gain of Chromosome 1q . . . . . . . . . . 228
11.3 Case Study 11.3: Multiple Myeloma with IgH Gene
Rearrangement with t(14;16) and Monosomies
of Chromosomes 13 and 16 . . . . . . . . . . . . . . . . . . . . . . . . . 230
11.4 Case Study 11.4: Multiple Myeloma
with Biallelic IgH Gene Rearrangement, t(4;14). . . . . . . . . 231
11.5 Case Study 11.5: Multiple Myeloma
with del(17) (p13.1) and Trisomy of Chromosome 11 . . . . 233
11.6 Case Study 11.6: Multiple Myeloma
with Trisomy Chromosome 17 and 1q Amplification . . . . . 234
11.7 Case Study 11.7: Multiple Myeloma
(Plasmablastic) with TP53 Gene Deletion
and Tetrasomies of Chromosomes 4, 11, 13, 14, and 1 . . . . 235
11.8 Case Study 11.8: Double-Hit Multiple
Myeloma with TP53 Gene Deletion,
Monosomy 13 and Gain of 1 q . . . . . . . . . . . . . . . . . . . . . . 238
11.9 Case Study 11.9: Triple-Hit Multiple
Myeloma with TP53 Gene Deletion, t(4;14)
with Gain of 1q and Deletion 1p . . . . . . . . . . . . . . . . . . . . . 240
11.10 Case Study 11.10: Triple-Hit Multiple
Myeloma with IgH Gene Rearrangement t(4;14),
TP53 Gene Deletion and Monosomy Chromosome 17,
Monosomy 13 and Gain of 1q . . . . . . . . . . . . . . . . . . . . . . . 242
Annexure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245

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