Contributions
Abstract: PB1721
Type: Publication Only
Session title: Myeloproliferative neoplasms - Clinical
Background
Asynchronous occurrence of myeloid/lymphoid malignancies has been previously described. Multiple malignant clones can arise from a cancer cell but accumulation of genetic events is not fully elucidated. We describe a rare case of consecutive AML, CLL and PV in which extended genetic profiling has been performed.
Aims
To report the concurrent presence of three hematologic malignancies in the same patient
Methods
Flow cytometry, cytogenetics and molecular analysis.
Results
A 69 years old male presented 5 years ago with lymphocytosis (ALC 15.0 K/ul). His medical history revealed acute myeloid leukemia (AML) M2 FAB, diagnosed 20 years earlier. He had received intensive chemotherapy and achieved complete response. Karyotype was not performed at that time. Lymphocytosis investigation was initiated and flow cytometry revealed a clonal B cell population expressing CD5+, CD23+, CD43+, CD200+, ROR1+, CD20dim, FMC7-, CD79b- and weak surface light chain immunoglobulin. Hemoglobin and platelet counts were within normal range. There were no palpable spleen, liver or B symptoms. Small axillar lymph nodes were present and patient was diagnosed with chronic lymphocytic leukemia (CLL), stage Rai I, Binet A. Cytogenetic analysis demonstrated 47,XY,+del(5)(q13q33)[2]/46,XY [21]. No NOTCH1 or TP53 mutations were present. IGHV genes were 88.8% mutated bearing the VDJ rearrangement IGHV1-3/IGHD2-15/IGHJ3. Del(13)(q) was detected by FISH in 61% of the cells, while here was no 17p or 11q deletion or trisomy 12. Within two years the patient developed progressive splenomegaly and subsequently received 6 cycles of chemo-immunochemotherapy with Obinutuzumab-chlorambucil. He achieved partial response (marrow MRD 1.9%, splenomegaly partially resolved). During regular follow-up visits, gradual increase in hemoglobin was noted (RBC 6.65 x 109 K/ul, Hb=17.1 g/dl, Ht=51.4%). Polycythemia Vera was suspected and JAK2 V617F mutation was found. Bone marrow biopsy revealed 75% cellularity, erythroid and megakaryocyte hyperplasia with groups of megakaryocytes, and blasts <5%. A 10% B lymphocyte infiltration was also noted. No BCR/ABL transcript was found. He was put on hydroxyurea and salicylic acid. Concurrent follicular thyroid cancer was diagnosed. NGS analysis was performed with Sophia Genetics Myeloid Panel on 3 subsequent samples from: (i)AML (ii) CLL and (iii) PV diagnosis and the results are as follows: (i) FLT3-ITD, NPM1 type A and IDH2 Arg140Gln mutations, (ii) the AML mutations disappeared, KRAS and DNMT3A mutations and a 3% JAK2V617F clone emerged and (iii) KRAS, DNMT3A and JAK2V617F clones expanded contributed probably to the PV phenotype. Interestingly, 2 TET2 and CEBPA mutations were stable in all three timepoints, possibly as CHIP, indicating a single cell of origin.
Conclusion
Herein, for the first time to our knowledge, we report the concurrent presence of three hematologic malignancies in the same patient. Common genetic background with clonal hematopoiesis may confer genetic instability, upon which distinct driver mutations arise, contributing to distinct phenotype.
Keyword(s): Acute myeloid leukemia, Chronic lymphocytic leukemia, Molecular markers, Polycythemia vera
Abstract: PB1721
Type: Publication Only
Session title: Myeloproliferative neoplasms - Clinical
Background
Asynchronous occurrence of myeloid/lymphoid malignancies has been previously described. Multiple malignant clones can arise from a cancer cell but accumulation of genetic events is not fully elucidated. We describe a rare case of consecutive AML, CLL and PV in which extended genetic profiling has been performed.
Aims
To report the concurrent presence of three hematologic malignancies in the same patient
Methods
Flow cytometry, cytogenetics and molecular analysis.
Results
A 69 years old male presented 5 years ago with lymphocytosis (ALC 15.0 K/ul). His medical history revealed acute myeloid leukemia (AML) M2 FAB, diagnosed 20 years earlier. He had received intensive chemotherapy and achieved complete response. Karyotype was not performed at that time. Lymphocytosis investigation was initiated and flow cytometry revealed a clonal B cell population expressing CD5+, CD23+, CD43+, CD200+, ROR1+, CD20dim, FMC7-, CD79b- and weak surface light chain immunoglobulin. Hemoglobin and platelet counts were within normal range. There were no palpable spleen, liver or B symptoms. Small axillar lymph nodes were present and patient was diagnosed with chronic lymphocytic leukemia (CLL), stage Rai I, Binet A. Cytogenetic analysis demonstrated 47,XY,+del(5)(q13q33)[2]/46,XY [21]. No NOTCH1 or TP53 mutations were present. IGHV genes were 88.8% mutated bearing the VDJ rearrangement IGHV1-3/IGHD2-15/IGHJ3. Del(13)(q) was detected by FISH in 61% of the cells, while here was no 17p or 11q deletion or trisomy 12. Within two years the patient developed progressive splenomegaly and subsequently received 6 cycles of chemo-immunochemotherapy with Obinutuzumab-chlorambucil. He achieved partial response (marrow MRD 1.9%, splenomegaly partially resolved). During regular follow-up visits, gradual increase in hemoglobin was noted (RBC 6.65 x 109 K/ul, Hb=17.1 g/dl, Ht=51.4%). Polycythemia Vera was suspected and JAK2 V617F mutation was found. Bone marrow biopsy revealed 75% cellularity, erythroid and megakaryocyte hyperplasia with groups of megakaryocytes, and blasts <5%. A 10% B lymphocyte infiltration was also noted. No BCR/ABL transcript was found. He was put on hydroxyurea and salicylic acid. Concurrent follicular thyroid cancer was diagnosed. NGS analysis was performed with Sophia Genetics Myeloid Panel on 3 subsequent samples from: (i)AML (ii) CLL and (iii) PV diagnosis and the results are as follows: (i) FLT3-ITD, NPM1 type A and IDH2 Arg140Gln mutations, (ii) the AML mutations disappeared, KRAS and DNMT3A mutations and a 3% JAK2V617F clone emerged and (iii) KRAS, DNMT3A and JAK2V617F clones expanded contributed probably to the PV phenotype. Interestingly, 2 TET2 and CEBPA mutations were stable in all three timepoints, possibly as CHIP, indicating a single cell of origin.
Conclusion
Herein, for the first time to our knowledge, we report the concurrent presence of three hematologic malignancies in the same patient. Common genetic background with clonal hematopoiesis may confer genetic instability, upon which distinct driver mutations arise, contributing to distinct phenotype.
Keyword(s): Acute myeloid leukemia, Chronic lymphocytic leukemia, Molecular markers, Polycythemia vera