LSD1 expression in normal and reactive hematopoiesis and hematopoietic and lymphoid neoplasms
| . | ICD-O-3 . | No. . | Intensity of expression . | Mean age (y) . | SD . | F . | % . | M . | % . | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Negative . | % . | Positive . | % . | |||||||||
| Hematopoiesis and hematopoietic neoplasms | ||||||||||||
| Normal | NA | 15 | 14 | 93.3 | 1 | 6.7 | 49.6 | 18.4 | 8 | 53.3 | 7 | 46.7 |
| Reactive | NA | 27 | 9 | 33.3 | 18 | 66.7 | 61.6 | 15.9 | 8 | 29.6 | 19 | 70.4 |
| MPN | 9875/3 CML | 19 | 13 | 68.4 | 6 | 31.6 | 61.6 | 11.2 | 9 | 47.4 | 10 | 52.6 |
| 9950/3 PV | 9 | 6 | 66.7 | 3 | 33.3 | 60.1 | 12.2 | 4 | 44.4 | 5 | 55.6 | |
| 9961/3 PMF | 31 | 13 | 41.9 | 18 | 58.1 | 65.2 | 14.5 | 16 | 51.6 | 15 | 48.4 | |
| 9962/3 ET | 12 | 7 | 58.3 | 5 | 41.7 | 68.2 | 11.6 | 7 | 58.3 | 5 | 41.7 | |
| Total | 71 | 39 | 54.9 | 32 | 45.1 | 64.1 | 13.0 | 36 | 50.7 | 35 | 49.3 | |
| MDS/MPN | 9945/3 CMML | 10 | 5 | 50.0 | 5 | 50.0 | 69.4 | 6.9 | 3 | 30.0 | 7 | 70.0 |
| MDS | Various, RA, RARS, RAEB I, RAEB II | 16 | 7 | 43.8 | 9 | 56.3 | 66.8 | 13.3 | 4 | 25.0 | 12 | 75.0 |
| AML | Various, AML with recurrent genetic abnormalities | 7 | 3 | 42.9 | 4 | 57.1 | 54.9 | 13.9 | 4 | 57.1 | 3 | 42.9 |
| 9895/3 AML with myelodysplasia related changes | 18 | 8 | 44.4 | 10 | 55.6 | 69.2 | 9.2 | 6 | 33.3 | 12 | 66.7 | |
| 9861/3 AML NOS | 13 | 6 | 46.2 | 7 | 53.8 | 64.1 | 13.3 | 9 | 69.2 | 4 | 30.8 | |
| NA, blast crisis from MPN | 7 | 7 | 100.0 | 0 | 0.0 | 68.9 | 5.4 | 2 | 28.6 | 5 | 71.4 | |
| Total | 45 | 24 | 53.3 | 21 | 46.7 | 65.4 | 11.7 | 21 | 46.7 | 24 | 53.3 | |
| ALL | 9811/3 B-ALL | 11 | 5 | 45.5 | 6 | 54.5 | 54.6 | 19.5 | 2 | 18.2 | 9 | 81.8 |
| 9837/3 T-ALL | 2 | 0 | 0.0 | 2 | 100.0 | 47.0 | 26.9 | 0 | 0.0 | 2 | 100.0 | |
| Total | 13 | 5 | 38.5 | 8 | 61.5 | 53.5 | 19.6 | 2 | 15.4 | 11 | 84.6 | |
| Lymphoid neoplasms | ||||||||||||
| Low-grade B-NHL | 9823/3 CLL/SLL | 36 | 36 | 100.0 | 0 | 0.0 | 66.8 | 10.7 | 12 | 33.3 | 24 | 66.7 |
| 9699/3 Marginal zone lymphoma | 21 | 16 | 76.2 | 5 | 23.8 | 64.2 | 12.6 | 10 | 47.6 | 11 | 52.4 | |
| 9690/3 Follicular lymphoma, grade 1,2 | 57 | 54 | 94.7 | 3 | 5.3 | 60.6 | 11.8 | 29 | 50.9 | 28 | 49.1 | |
| 9673/3 Mantle cell lymphoma | 33 | 22 | 66.7 | 11 | 33.3 | 68.2 | 8.8 | 8 | 24.2 | 25 | 75.8 | |
| Total | 147 | 128 | 87.1 | 19 | 12.9 | 64.3 | 11.4 | 59 | 40.1 | 88 | 59.9 | |
| High-grade B-NHL | ||||||||||||
| 9690/3 Follicular lymphoma, grade 3a,3b | 20 | 15 | 75.0 | 5 | 25.0 | 59.7 | 16.7 | 14 | 70.0 | 6 | 30.0 | |
| 9680/3 DLBCL NOS | 102 | 63 | 61.8 | 39 | 38.2 | 62.2 | 17.3 | 48 | 47.1 | 54 | 52.9 | |
| 9687/3 Burkitt lymphoma | 9 | 1 | 11.1 | 8 | 88.9 | 56.7 | 27.5 | 3 | 33.3 | 6 | 66.7 | |
| Total | 131 | 79 | 60.3 | 52 | 39.7 | 61.4 | 17.9 | 65 | 49.6 | 66 | 50.4 | |
| B-NHL | Total | 278 | 207 | 74.5 | 71 | 25.5 | 63.0 | 14.9 | 124 | 44.6 | 154 | 55.4 |
| T-NHL | ||||||||||||
| 9705/3 AITL | 8 | 2 | 25.0 | 6 | 75.0 | 66.6 | 13.3 | 4 | 50.0 | 4 | 50.0 | |
| 9714/3 ALCL | 6 | 0 | 0.0 | 6 | 100.0 | 44.2 | 26.2 | 2 | 33.3 | 4 | 66.7 | |
| 9705/3 PTCL NOS | 7 | 5 | 71.4 | 2 | 28.6 | 76.7 | 6.8 | 5 | 71.4 | 2 | 28.6 | |
| Total | 21 | 7 | 33.3 | 14 | 66.7 | 62.5 | 16.7 | 11 | 52.4 | 10 | 47.6 | |
| HL | ||||||||||||
| 9663/3 Nodular sclerosing type | 36 | 14 | 38.9 | 22 | 61.1 | 34.6 | 19.0 | 21 | 58.3 | 15 | 41.7 | |
| 9652/3 Mixed cellularity subtype | 10 | 2 | 20.0 | 8 | 80.0 | 31,8 | 14.6 | 5 | 50.0 | 5 | 50.0 | |
| 9651/3 Lymphocyte-rich/lymphocyte-predominant | 9 | 1 | 11.1 | 8 | 88.9 | 50.7 | 23.6 | 5 | 55.6 | 4 | 44.4 | |
| Total | 55 | 17 | 30.9 | 38 | 69.1 | 36.8 | 19.8 | 31 | 56.4 | 24 | 43.6 | |
| . | ICD-O-3 . | No. . | Intensity of expression . | Mean age (y) . | SD . | F . | % . | M . | % . | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Negative . | % . | Positive . | % . | |||||||||
| Hematopoiesis and hematopoietic neoplasms | ||||||||||||
| Normal | NA | 15 | 14 | 93.3 | 1 | 6.7 | 49.6 | 18.4 | 8 | 53.3 | 7 | 46.7 |
| Reactive | NA | 27 | 9 | 33.3 | 18 | 66.7 | 61.6 | 15.9 | 8 | 29.6 | 19 | 70.4 |
| MPN | 9875/3 CML | 19 | 13 | 68.4 | 6 | 31.6 | 61.6 | 11.2 | 9 | 47.4 | 10 | 52.6 |
| 9950/3 PV | 9 | 6 | 66.7 | 3 | 33.3 | 60.1 | 12.2 | 4 | 44.4 | 5 | 55.6 | |
| 9961/3 PMF | 31 | 13 | 41.9 | 18 | 58.1 | 65.2 | 14.5 | 16 | 51.6 | 15 | 48.4 | |
| 9962/3 ET | 12 | 7 | 58.3 | 5 | 41.7 | 68.2 | 11.6 | 7 | 58.3 | 5 | 41.7 | |
| Total | 71 | 39 | 54.9 | 32 | 45.1 | 64.1 | 13.0 | 36 | 50.7 | 35 | 49.3 | |
| MDS/MPN | 9945/3 CMML | 10 | 5 | 50.0 | 5 | 50.0 | 69.4 | 6.9 | 3 | 30.0 | 7 | 70.0 |
| MDS | Various, RA, RARS, RAEB I, RAEB II | 16 | 7 | 43.8 | 9 | 56.3 | 66.8 | 13.3 | 4 | 25.0 | 12 | 75.0 |
| AML | Various, AML with recurrent genetic abnormalities | 7 | 3 | 42.9 | 4 | 57.1 | 54.9 | 13.9 | 4 | 57.1 | 3 | 42.9 |
| 9895/3 AML with myelodysplasia related changes | 18 | 8 | 44.4 | 10 | 55.6 | 69.2 | 9.2 | 6 | 33.3 | 12 | 66.7 | |
| 9861/3 AML NOS | 13 | 6 | 46.2 | 7 | 53.8 | 64.1 | 13.3 | 9 | 69.2 | 4 | 30.8 | |
| NA, blast crisis from MPN | 7 | 7 | 100.0 | 0 | 0.0 | 68.9 | 5.4 | 2 | 28.6 | 5 | 71.4 | |
| Total | 45 | 24 | 53.3 | 21 | 46.7 | 65.4 | 11.7 | 21 | 46.7 | 24 | 53.3 | |
| ALL | 9811/3 B-ALL | 11 | 5 | 45.5 | 6 | 54.5 | 54.6 | 19.5 | 2 | 18.2 | 9 | 81.8 |
| 9837/3 T-ALL | 2 | 0 | 0.0 | 2 | 100.0 | 47.0 | 26.9 | 0 | 0.0 | 2 | 100.0 | |
| Total | 13 | 5 | 38.5 | 8 | 61.5 | 53.5 | 19.6 | 2 | 15.4 | 11 | 84.6 | |
| Lymphoid neoplasms | ||||||||||||
| Low-grade B-NHL | 9823/3 CLL/SLL | 36 | 36 | 100.0 | 0 | 0.0 | 66.8 | 10.7 | 12 | 33.3 | 24 | 66.7 |
| 9699/3 Marginal zone lymphoma | 21 | 16 | 76.2 | 5 | 23.8 | 64.2 | 12.6 | 10 | 47.6 | 11 | 52.4 | |
| 9690/3 Follicular lymphoma, grade 1,2 | 57 | 54 | 94.7 | 3 | 5.3 | 60.6 | 11.8 | 29 | 50.9 | 28 | 49.1 | |
| 9673/3 Mantle cell lymphoma | 33 | 22 | 66.7 | 11 | 33.3 | 68.2 | 8.8 | 8 | 24.2 | 25 | 75.8 | |
| Total | 147 | 128 | 87.1 | 19 | 12.9 | 64.3 | 11.4 | 59 | 40.1 | 88 | 59.9 | |
| High-grade B-NHL | ||||||||||||
| 9690/3 Follicular lymphoma, grade 3a,3b | 20 | 15 | 75.0 | 5 | 25.0 | 59.7 | 16.7 | 14 | 70.0 | 6 | 30.0 | |
| 9680/3 DLBCL NOS | 102 | 63 | 61.8 | 39 | 38.2 | 62.2 | 17.3 | 48 | 47.1 | 54 | 52.9 | |
| 9687/3 Burkitt lymphoma | 9 | 1 | 11.1 | 8 | 88.9 | 56.7 | 27.5 | 3 | 33.3 | 6 | 66.7 | |
| Total | 131 | 79 | 60.3 | 52 | 39.7 | 61.4 | 17.9 | 65 | 49.6 | 66 | 50.4 | |
| B-NHL | Total | 278 | 207 | 74.5 | 71 | 25.5 | 63.0 | 14.9 | 124 | 44.6 | 154 | 55.4 |
| T-NHL | ||||||||||||
| 9705/3 AITL | 8 | 2 | 25.0 | 6 | 75.0 | 66.6 | 13.3 | 4 | 50.0 | 4 | 50.0 | |
| 9714/3 ALCL | 6 | 0 | 0.0 | 6 | 100.0 | 44.2 | 26.2 | 2 | 33.3 | 4 | 66.7 | |
| 9705/3 PTCL NOS | 7 | 5 | 71.4 | 2 | 28.6 | 76.7 | 6.8 | 5 | 71.4 | 2 | 28.6 | |
| Total | 21 | 7 | 33.3 | 14 | 66.7 | 62.5 | 16.7 | 11 | 52.4 | 10 | 47.6 | |
| HL | ||||||||||||
| 9663/3 Nodular sclerosing type | 36 | 14 | 38.9 | 22 | 61.1 | 34.6 | 19.0 | 21 | 58.3 | 15 | 41.7 | |
| 9652/3 Mixed cellularity subtype | 10 | 2 | 20.0 | 8 | 80.0 | 31,8 | 14.6 | 5 | 50.0 | 5 | 50.0 | |
| 9651/3 Lymphocyte-rich/lymphocyte-predominant | 9 | 1 | 11.1 | 8 | 88.9 | 50.7 | 23.6 | 5 | 55.6 | 4 | 44.4 | |
| Total | 55 | 17 | 30.9 | 38 | 69.1 | 36.8 | 19.8 | 31 | 56.4 | 24 | 43.6 | |
To determine LSD1 expression in hematopoiesis and hematopoietic neoplasms, bone marrow trephine biopsies were decalcified and immunostained by using a monoclonal anti-mouse antibody against LSD1 (1:500; Novus Biologicals, Littleton, CO). Intensity of expression was assessed as either none or background (negative) or moderate or strong (positive). Expression was positive in myeloproliferative neoplasms (MPNs), myelodysplastic syndrome (MDS), normal bone marrow, and reactive bone marrow if 1 to 3 lineages showed intensive expression, which was most often observed in the erythroid and megakaryocytic lineage. In acute leukemias, blasts only were scored. To determine LSD1 expression in lymphoid neoplasms, tissue microarrays of lymphoid tissues were immunostained with anti-mouse antibody against LSD1 (1:2000; Novus Biologicals). Samples with expression in less than 10% of tumor cells were scored as negative; moderate or strong staining in more than 10% of tumor cells was scored positive. Tissue microarrays were constructed from lymphoma tissue samples reclassified according the World Health Organization 2008 classification and were obtained from the archives of the Institute of Pathology at the University of Bonn as described.9 LSD1 was expressed in 75 (48.4%) of 155 hematopoietic neoplasms but in only 123 (34.7%) of 354 lymphoid neoplasms (Pearson χ2 test P < .004). Statistically significant differences were also found in expression of normal and reactive bone marrow (Fisher’s exact test P < .001) and normal and neoplastic bone marrow (Fisher’s exact test, P < .002). Among lymphoid neoplasms, there was a significant difference between high-grade and low-grade B-NHLs (Pearson χ2 test P < .001). Expression in B-NHLs combined differed from T-cell NHLs (T-NHLs) as well as from Hodgkin lymphomas (HLs) (Pearson χ2 test, P < .001 in both cases). All calculations were performed by using SPSS Statistics for Windows, Version 20 (IBM, Armonk, NY).
AITL, angioimmunoblastic T-cell lymphoma; ALCL, anaplastic large-cell lymphoma; ALL, acute lymphoblastic leukemia; B-ALL, B-cell ALL; CLL, chronic lymphocytic leukemia, B-cell type; CML, chronic myelogenous leukemia; CMML, chronic myelomonocytic leukemia; DLBCL, diffuse large B-cell lymphoma; ET, essential thrombocythemia; F, female; ICD-O-03, International Classification of Diseases-Oncology, third edition; M, male; NA, not applicable; NOS, not otherwise specified; PMF, primary myelofibrosis; PTCL, peripheral T-cell-lymphoma; PV, polycythemia vera; RA, refractory anemia; RAEB, refractory anemia with excess blasts; RARS, refractory anemia with ringed sideroblasts; SLL, small lymphocytic lymphoma; SD, standard deviation; T-ALL, T-cell ALL.